PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 22490993-6 2012 Metformin also plays a direct inhibition of cancer cell growth via the inhibitory effects of AMP-activated protein kinase on the mTOR pathway, which regulates cell growth and proliferation. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 129-133 22343549-8 2012 Metformin treatment blocked ghrelin-induced activation of hypothalamic AMPK/ACC/Raptor and restored mTOR activity without affecting S6K phosphorylation. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 100-104 22994747-3 2012 Our research indicates that metformin displays anticancer activity against HCC through inhibition of the mTOR translational pathway in an AMPK-independent manner, leading to G1 arrest in the cell-cycle and subsequent cell apoptosis through the mitochondrion-dependent pathway. Metformin 28-37 mechanistic target of rapamycin kinase Homo sapiens 105-109 22080879-2 2012 LY294002 (PI3K inhibitor) and metformin (5"-adenosine monophosphate [AMP]-activated protein kinase [AMPK] activator) are 2 drugs that were known to inhibit mTOR expression through the AKT-dependent and AKT-independent pathways, respectively. Metformin 30-39 mechanistic target of rapamycin kinase Homo sapiens 156-160 22080879-7 2012 RESULTS: Our study showed that LY294002 and metformin in combination could simultaneously enhance the repression of the PI3K/AKT/mTOR pathway and the activation of the AMPK/ACC pathway. Metformin 44-53 mechanistic target of rapamycin kinase Homo sapiens 129-133 22863784-9 2012 Preincubation of endothelial cells with AGE-BSA and metformin, an anti-diabetic drug known to have an mTOR inhibition effect, significantly reduced AGE-stimulated LOX-1 expression. Metformin 52-61 mechanistic target of rapamycin kinase Homo sapiens 102-106 22343549-10 2012 CONCLUSION: Metformin could reduce food intake by preventing ghrelin-induced AMPK signalling and mTOR inhibition in the hypotalamus. Metformin 12-21 mechanistic target of rapamycin kinase Homo sapiens 97-101 22500211-5 2012 Both metformin and ionizing radiation activated AMPK leading to inactivation of mTOR and suppression of its downstream effectors such as S6K1 and 4EBP1, a crucial signaling pathway for proliferation and survival of cancer cells, in vitro as well as in the in vivo tumors. Metformin 5-14 mechanistic target of rapamycin kinase Homo sapiens 80-84 22500211-6 2012 CONCLUSION: Metformin kills and radiosensitizes cancer cells and eradicates radioresistant cancer stem cells by activating AMPK and suppressing mTOR. Metformin 12-21 mechanistic target of rapamycin kinase Homo sapiens 144-148 22203527-2 2011 Metformin"s molecular targets in cancer cells (e.g., mTOR, HER2) are similar to those currently being used for directed cancer therapy. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 53-57 22021366-3 2011 We report that AMPK activators, such as metformin and 5-aminoimidazole-4-carboxamide ribonucleotide, suppress activation of the mTOR pathway in BCR-ABL-expressing cells. Metformin 40-49 mechanistic target of rapamycin kinase Homo sapiens 128-132 21631893-6 2011 The major molecular targets of metformin are the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) signaling and mammalian target of rapamycin (mTOR) pathways, which are central in the regulation of cellular energy homeostasis and play a crucial role in the control of cell division and cell proliferation. Metformin 31-40 mechanistic target of rapamycin kinase Homo sapiens 122-151 21631893-6 2011 The major molecular targets of metformin are the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) signaling and mammalian target of rapamycin (mTOR) pathways, which are central in the regulation of cellular energy homeostasis and play a crucial role in the control of cell division and cell proliferation. Metformin 31-40 mechanistic target of rapamycin kinase Homo sapiens 153-157 22015290-3 2011 Metformin, a commonly used diabetes drug, lowers insulin in non-breast diabetic cancer patients, likely by reducing hepatic gluconeogenesis; it also appears to have potential insulin independent direct effects on tumor cells which are mediated by activation of AMPK with downstream inhibition of mTOR. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 296-300 22067284-5 2011 Since persistent constitutive DNA replication stress, particularly when paralleled by mTOR signaling, is considered to be the major cause of aging, the present findings are consistent with the notion that metformin, by reducing both DNA replication stress and mTOR-signaling, slows down aging and/or cell senescence processes. Metformin 205-214 mechanistic target of rapamycin kinase Homo sapiens 86-90 22067284-5 2011 Since persistent constitutive DNA replication stress, particularly when paralleled by mTOR signaling, is considered to be the major cause of aging, the present findings are consistent with the notion that metformin, by reducing both DNA replication stress and mTOR-signaling, slows down aging and/or cell senescence processes. Metformin 205-214 mechanistic target of rapamycin kinase Homo sapiens 260-264 21540236-0 2011 Metformin, independent of AMPK, induces mTOR inhibition and cell-cycle arrest through REDD1. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 40-44 21655990-12 2011 By ingenuity pathway analysis, the tumour necrosis factor receptor 1 (TNFR1) signaling pathway was most affected by metformin: TGFB and MEKK were upregulated and cdc42 downregulated; mTOR and AMPK pathways were also affected. Metformin 116-125 mechanistic target of rapamycin kinase Homo sapiens 183-187 21552292-6 2011 Furthermore, metformin suppressed the phosphorylation of Akt/protein kinase B (AKT) and mammalian target of rapamycin (mTOR) in response to pressure overload in wild type mice, but not in AMPKalpha2-/- mice. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 88-117 21552292-6 2011 Furthermore, metformin suppressed the phosphorylation of Akt/protein kinase B (AKT) and mammalian target of rapamycin (mTOR) in response to pressure overload in wild type mice, but not in AMPKalpha2-/- mice. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 119-123 21168492-0 2011 Metformin promotes progesterone receptor expression via inhibition of mammalian target of rapamycin (mTOR) in endometrial cancer cells. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 70-99 21168492-0 2011 Metformin promotes progesterone receptor expression via inhibition of mammalian target of rapamycin (mTOR) in endometrial cancer cells. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 101-105 21540236-2 2011 Many studies show that metformin inhibits cancer cell viability through the inhibition of mTOR. Metformin 23-32 mechanistic target of rapamycin kinase Homo sapiens 90-94 21540236-4 2011 We identified REDD1 (also known as DDIT4 and RTP801), a negative regulator of mTOR, as a new molecular target of metformin. Metformin 113-122 mechanistic target of rapamycin kinase Homo sapiens 78-82 21540236-6 2011 REDD1 invalidation, using siRNA or REDD1(-/-) cells, abrogates metformin inhibition of mTOR. Metformin 63-72 mechanistic target of rapamycin kinase Homo sapiens 87-91 21840335-25 2011 Promising candidates are those that intersect with the critical signaling pathways identified above and include biguanides such as metformin that target the insulin signaling pathway, stilbenes (e.g. resveratrol) that affect sirtuin activity and drugs such as rapamycin that interact with mTOR signaling. Metformin 131-140 mechanistic target of rapamycin kinase Homo sapiens 289-293 21680296-3 2011 Metformin activates the AMP-activated protein kinase (AMPK) pathway, a major sensor of the energy status of the cell and an inhibitor of mammalian target of rapamycin (mTOR) catalytic activity, inducing a decrease in blood glucose by decreasing hepatic gluconeogenesis and stimulating glucose uptake in the muscle. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 137-166 21680296-3 2011 Metformin activates the AMP-activated protein kinase (AMPK) pathway, a major sensor of the energy status of the cell and an inhibitor of mammalian target of rapamycin (mTOR) catalytic activity, inducing a decrease in blood glucose by decreasing hepatic gluconeogenesis and stimulating glucose uptake in the muscle. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 168-172 21270604-8 2011 In addition, medroxyprogesterone acetate-induced mTOR phosphorylation was blocked by metformin. Metformin 85-94 mechanistic target of rapamycin kinase Homo sapiens 49-53 21465524-7 2011 Metformin also increased the phosphorylation of c-Jun N-terminal kinase (JNK)-c-Jun and mammalian target of rapamycin (mTOR)-p70S6 kinase pathways. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 88-117 21465524-7 2011 Metformin also increased the phosphorylation of c-Jun N-terminal kinase (JNK)-c-Jun and mammalian target of rapamycin (mTOR)-p70S6 kinase pathways. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 119-123 21532889-6 2011 Metformin-induced activation of AMPK/mTOR pathway was accompanied by decreased microvessel density and vascular endothelial growth factor expression. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 37-41 21262823-5 2011 We find that metformin stimulates AMPK, resulting in inhibition of both CFTR and the mTOR pathways. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 85-89 21470407-5 2011 Moreover, metformin may exhibit direct inhibitory effects on cancer cells by inhibiting mammalian target of rapamycin (mTOR) signaling and protein synthesis. Metformin 10-19 mechanistic target of rapamycin kinase Homo sapiens 88-117 21470407-5 2011 Moreover, metformin may exhibit direct inhibitory effects on cancer cells by inhibiting mammalian target of rapamycin (mTOR) signaling and protein synthesis. Metformin 10-19 mechanistic target of rapamycin kinase Homo sapiens 119-123 21270604-9 2011 Metformin abolishes mTOR phosphorylation and inhibits GloI expression, attenuating proliferation and inducing apoptosis in progestin-resistant Ishikawa cells. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 20-24 20810671-2 2010 (beginning on page 1066 in this issue of the journal) assessing the efficacy of the antidiabetes drug metformin in a mouse model of lung carcinogenesis suggests protective effects via two possible avenues: Decreased circulating insulin and insulin-like growth factor levels and energy stress leading to inhibition of mammalian target of rapamycin signaling. Metformin 102-111 mechanistic target of rapamycin kinase Homo sapiens 317-346 21084384-7 2011 A 24 h exposure to metformin stimulated AMP-activated protein kinase (AMPK), suppressed activation of translation factors- both the mammalian target of rapamycin (mTOR; also known as mechanistic target of rapamycin, MTOR)-dependent ones (eukaryotic initiation factor 4E-binding protein 1 and ribosomal protein S6) and the mTOR-independent eukaryotic elongation factor 2-, and inhibited protein synthesis; a 72 h exposure resulted in 50% dead cells. Metformin 19-28 mechanistic target of rapamycin kinase Homo sapiens 132-161 21084384-7 2011 A 24 h exposure to metformin stimulated AMP-activated protein kinase (AMPK), suppressed activation of translation factors- both the mammalian target of rapamycin (mTOR; also known as mechanistic target of rapamycin, MTOR)-dependent ones (eukaryotic initiation factor 4E-binding protein 1 and ribosomal protein S6) and the mTOR-independent eukaryotic elongation factor 2-, and inhibited protein synthesis; a 72 h exposure resulted in 50% dead cells. Metformin 19-28 mechanistic target of rapamycin kinase Homo sapiens 163-167 21084384-7 2011 A 24 h exposure to metformin stimulated AMP-activated protein kinase (AMPK), suppressed activation of translation factors- both the mammalian target of rapamycin (mTOR; also known as mechanistic target of rapamycin, MTOR)-dependent ones (eukaryotic initiation factor 4E-binding protein 1 and ribosomal protein S6) and the mTOR-independent eukaryotic elongation factor 2-, and inhibited protein synthesis; a 72 h exposure resulted in 50% dead cells. Metformin 19-28 mechanistic target of rapamycin kinase Homo sapiens 216-220 21084384-7 2011 A 24 h exposure to metformin stimulated AMP-activated protein kinase (AMPK), suppressed activation of translation factors- both the mammalian target of rapamycin (mTOR; also known as mechanistic target of rapamycin, MTOR)-dependent ones (eukaryotic initiation factor 4E-binding protein 1 and ribosomal protein S6) and the mTOR-independent eukaryotic elongation factor 2-, and inhibited protein synthesis; a 72 h exposure resulted in 50% dead cells. Metformin 19-28 mechanistic target of rapamycin kinase Homo sapiens 322-326 21098287-0 2010 Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling. Metformin 10-19 mechanistic target of rapamycin kinase Homo sapiens 52-56 21349801-7 2011 These new encouraging experimental data supporting the anti-cancer effects of metformin urgently require further clinical studies in order to establish its use as a synergistic therapy targeting the AMPK/mTOR signaling pathway. Metformin 78-87 mechanistic target of rapamycin kinase Homo sapiens 204-208 19822355-13 2010 In parallel, treatment with metformin decreased phosphorylation of S6 protein, a key target of the mTOR pathway. Metformin 28-37 mechanistic target of rapamycin kinase Homo sapiens 99-103 20135346-2 2010 Adenosine 5"- monophosphate-activated protein kinase (AMPK) activators such as metformin have similar actions, in keeping with the TSC2/1 pathway linking activation of AMPK to inhibition of mTOR. Metformin 79-88 mechanistic target of rapamycin kinase Homo sapiens 190-194 20363874-3 2010 The AMPK activator metformin stimulated AMPK Thr172 phosphorylation and inhibited IGF-I-stimulated phosphorylation of Akt/tuberous sclerosis 2 (TSC2)/mammalian target of rapamycin (mTOR)/p70S6 kinase (p70S6K). Metformin 19-28 mechanistic target of rapamycin kinase Homo sapiens 150-179 20363874-3 2010 The AMPK activator metformin stimulated AMPK Thr172 phosphorylation and inhibited IGF-I-stimulated phosphorylation of Akt/tuberous sclerosis 2 (TSC2)/mammalian target of rapamycin (mTOR)/p70S6 kinase (p70S6K). Metformin 19-28 mechanistic target of rapamycin kinase Homo sapiens 181-185 20135346-7 2010 Although both rapamycin and metformin inhibit mTOR (the former directly and the latter through AMPK signaling), our results demonstrate previously unrecognized differences between these agents. Metformin 28-37 mechanistic target of rapamycin kinase Homo sapiens 46-50 20564343-2 2010 Adenosine monophosphate-activated protein kinase (AMPK) is known to be activated by metformin and to inhibit the mammalian target of rapamycin (mTOR) pathway. Metformin 84-93 mechanistic target of rapamycin kinase Homo sapiens 144-148 20465505-4 2010 There is also a growing interest in the use of metformin, which has been shown to possess antitumor activity resulting from activation of AMP-activated protein kinase and subsequent inhibiton of mTOR, as well as from decreased circulating insulin levels. Metformin 47-56 mechanistic target of rapamycin kinase Homo sapiens 195-199 20126541-8 2010 Administration of the glycolytic inhibitor 2-deoxy-D-glucose (2DG) or the mitochondrial toxin and anti-Type II Diabetes drug, metformin, or AMP mimetic AICAR results in activation of AMPK, repression of the mTOR pathway and prevents maintenance of Late-Phase LTP (L-LTP). Metformin 126-135 mechanistic target of rapamycin kinase Homo sapiens 207-211 19858375-0 2009 If mammalian target of metformin indirectly is mammalian target of rapamycin, then the insulin-like growth factor-1 receptor axis will audit the efficacy of metformin in cancer clinical trials. Metformin 23-32 mechanistic target of rapamycin kinase Homo sapiens 47-76 19858366-0 2009 LKB1 and mammalian target of rapamycin as predictive factors for the anticancer efficacy of metformin. Metformin 92-101 mechanistic target of rapamycin kinase Homo sapiens 9-38 19858375-0 2009 If mammalian target of metformin indirectly is mammalian target of rapamycin, then the insulin-like growth factor-1 receptor axis will audit the efficacy of metformin in cancer clinical trials. Metformin 157-166 mechanistic target of rapamycin kinase Homo sapiens 47-76 19560877-9 2009 Metformin causes Her-2 suppression via the inhibition of mTOR in breast cancer cells. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 57-61 19679549-3 2009 Metformin, the most widely used drug in the treatment of type 2 diabetes, activates AMP kinase (AMPK), which negatively regulates mTOR. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 130-134 19574203-6 2009 The unexpected ability of the anti-type II diabetes drug metformin to inactivate mTOR and decrease p70S6K1 activity further reveals that this biguanide, generally considered non-toxic and remarkably inexpensive, might be considered for new combinatorial lapatinib-based protocols in HER2-overexpressing breast cancer patients. Metformin 57-66 mechanistic target of rapamycin kinase Homo sapiens 81-85 19106626-0 2009 The antidiabetic drug metformin suppresses HER2 (erbB-2) oncoprotein overexpression via inhibition of the mTOR effector p70S6K1 in human breast carcinoma cells. Metformin 22-31 mechanistic target of rapamycin kinase Homo sapiens 106-110 19106626-13 2009 The importance of mTOR/p70S6K1-sensed ROS status at mediating the anti-oncogenic effects of metformin might represent a previously unrecognized linkage molecularly connecting its anti-aging and anti-cancer actions. Metformin 92-101 mechanistic target of rapamycin kinase Homo sapiens 18-22 18803638-9 2008 In contrast, metformin activated AMPK in the intestinal polyps, resulting in the inhibition of the activation of mammalian target of rapamycin, which play important roles in the protein synthesis machinery. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 113-142 17698034-8 2007 Metformin treatment of the hepatocytes resulted in activation of the AMP-activated kinase, attenuation of the mTOR/S6K1 pathway, reduction of IRS-1 phosphorylation, and a leftward shift in the insulin dose-response curve for PKB activation. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 110-114 18678646-6 2008 Treatment of both primary cells and cancer cell lines with rapamycin, metformin, and pyrvinium resulted in an increase in p73 levels, as did RNA interference-mediated knockdown of mTOR. Metformin 70-79 mechanistic target of rapamycin kinase Homo sapiens 180-184 18006825-0 2007 Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 19-48 18006825-8 2007 The decrease in translation caused by metformin was associated with mammalian target of rapamycin (mTOR) inhibition, and a decrease in the phosphorylation of S6 kinase, ribosomal protein S6, and eIF4E-binding protein 1. Metformin 38-47 mechanistic target of rapamycin kinase Homo sapiens 68-97 18006825-8 2007 The decrease in translation caused by metformin was associated with mammalian target of rapamycin (mTOR) inhibition, and a decrease in the phosphorylation of S6 kinase, ribosomal protein S6, and eIF4E-binding protein 1. Metformin 38-47 mechanistic target of rapamycin kinase Homo sapiens 99-103 18006825-11 2007 These results show that metformin-mediated AMPK activation leads to inhibition of mTOR and a reduction in translation initiation, thus providing a possible mechanism of action of metformin in the inhibition of cancer cell growth. Metformin 24-33 mechanistic target of rapamycin kinase Homo sapiens 82-86 18006825-11 2007 These results show that metformin-mediated AMPK activation leads to inhibition of mTOR and a reduction in translation initiation, thus providing a possible mechanism of action of metformin in the inhibition of cancer cell growth. Metformin 179-188 mechanistic target of rapamycin kinase Homo sapiens 82-86 33762564-0 2021 Retracted: Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway. Metformin 34-43 mechanistic target of rapamycin kinase Homo sapiens 148-177 16354680-7 2006 Knockdown of Raptor as well as activators of the LKB1/AMPK pathway, such as the widely used antidiabetic compound metformin, suppress IRS-1 Ser636/639 phosphorylation and reverse mTOR-mediated inhibition on PI3-kinase/Akt signaling. Metformin 114-123 mechanistic target of rapamycin kinase Homo sapiens 179-183 33762564-0 2021 Retracted: Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway. Metformin 34-43 mechanistic target of rapamycin kinase Homo sapiens 179-183 33762564-2 2021 Reference: Fengli Zhang, Huixiao Chen, Jing Du, Bin Wang, Lixiao Yang: Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway. Metformin 94-103 mechanistic target of rapamycin kinase Homo sapiens 208-237 33762564-2 2021 Reference: Fengli Zhang, Huixiao Chen, Jing Du, Bin Wang, Lixiao Yang: Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway. Metformin 94-103 mechanistic target of rapamycin kinase Homo sapiens 239-243 33768205-2 2020 Therapeutic activation of AMPK by metformin could inhibit cyst enlargement by inhibition of both the mammalian target of rapamycin pathway and fluid secretion via the CFTR chloride channel. Metformin 34-43 mechanistic target of rapamycin kinase Homo sapiens 101-130 33807522-9 2021 Metformin suppresses the mechanistic target of rapamycin (mTOR) by activating AMPK in pre-neoplastic cells, which leads to suppression of cell growth and an increase in apoptosis in pre-neoplastic cells. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 25-56 33807522-9 2021 Metformin suppresses the mechanistic target of rapamycin (mTOR) by activating AMPK in pre-neoplastic cells, which leads to suppression of cell growth and an increase in apoptosis in pre-neoplastic cells. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 58-62 34432352-0 2021 Pretreatment with metformin prevents microcystin-LR-induced tau hyperphosphorylation via mTOR-dependent PP2A and GSK-3beta activation. Metformin 18-27 mechanistic target of rapamycin kinase Homo sapiens 89-93 34637881-5 2022 We then addressed metformin"s effects on the AMPK-AKT-mTOR-HIFA pathway on two human primary cultures: one from a VHL-mutant PCC and other from a sporadic PCC. Metformin 18-27 mechanistic target of rapamycin kinase Homo sapiens 54-58 20668229-2 2010 We show in our current study that the LKB1/AMPK/TSC tumor suppressor axis is functional in AML and can be activated by the biguanide molecule metformin, resulting in a specific inhibition of mammalian target of rapamycin (mTOR) catalytic activity. Metformin 142-151 mechanistic target of rapamycin kinase Homo sapiens 191-220 20668229-2 2010 We show in our current study that the LKB1/AMPK/TSC tumor suppressor axis is functional in AML and can be activated by the biguanide molecule metformin, resulting in a specific inhibition of mammalian target of rapamycin (mTOR) catalytic activity. Metformin 142-151 mechanistic target of rapamycin kinase Homo sapiens 222-226 34628168-6 2021 Interestingly, metformin, an extensively used antidiabetic drug, inhibits mTOR by affecting the activity of AMPK. Metformin 15-24 mechanistic target of rapamycin kinase Homo sapiens 74-78 34432352-5 2021 The effect of metformin on PP2A activity was dependent on the inhibition of mTOR in MC-LR-treated SH-SY5Y cells. Metformin 14-23 mechanistic target of rapamycin kinase Homo sapiens 76-80 34944598-0 2021 Metformin Improves Stemness of Human Adipose-Derived Stem Cells by Downmodulation of Mechanistic Target of Rapamycin (mTOR) and Extracellular Signal-Regulated Kinase (ERK) Signaling. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 85-116 34664036-7 2021 Maintaining proper blood glucose levels using oral antidiabetic drugs like Metformin reduced the detrimental effects of COVID-19 by different possible mechanisms such as Metformin-mediated anti-inflammatory and immunomodulatory activities; effect on viral entry and ACE2 stability; inhibition of virus infection; alters virus survival and endosomal pH; mTOR inhibition; and influence on gut microbiota. Metformin 75-84 mechanistic target of rapamycin kinase Homo sapiens 353-357 34944598-0 2021 Metformin Improves Stemness of Human Adipose-Derived Stem Cells by Downmodulation of Mechanistic Target of Rapamycin (mTOR) and Extracellular Signal-Regulated Kinase (ERK) Signaling. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 118-122 34944598-8 2021 Investigating the possible underlying mechanism, we observed a decrease in the mTOR and ERK activity in metformin-treated ASCs. Metformin 104-113 mechanistic target of rapamycin kinase Homo sapiens 79-83 34944598-10 2021 We conclude that metformin treatment improves ASCs stemness by reducing mTOR and ERK signaling and enhancing autophagy. Metformin 17-26 mechanistic target of rapamycin kinase Homo sapiens 72-76 34481229-5 2021 SC proliferation-inhibiting effect of metformin exposure was regulated by decreasing adenosine triphosphate level and respiratory enzyme activity in the mitochondria; this process was possibly mediated by the adenosine monophosphate-activated protein kinase (AMPK)/tuberous sclerosis complex 2 (TSC2)/mammalian target of rapamycin (mTOR) signaling pathway, which was regulated by the down-expressed miR-1764 and by the decreased antioxidant enzyme activity and excessive reactive oxygen species generation. Metformin 38-47 mechanistic target of rapamycin kinase Homo sapiens 301-330 34753372-3 2022 One of the medications widely used in the treatment of T2DM is biguanide derivative, metformin, which exerts promising anticancer properties principally through activation of adenosine monophosphate kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) pathways. Metformin 85-94 mechanistic target of rapamycin kinase Homo sapiens 231-260 34753372-3 2022 One of the medications widely used in the treatment of T2DM is biguanide derivative, metformin, which exerts promising anticancer properties principally through activation of adenosine monophosphate kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) pathways. Metformin 85-94 mechanistic target of rapamycin kinase Homo sapiens 262-266 34607979-7 2021 Metformin diminished the phosphorylation of mTOR, p70S6K and 4E-BP1 by accelerating adenosine monophosphateactivated kinase (AMPK) in HeLa cancer cells, but it did not affect other cell lines. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 44-48 34481229-5 2021 SC proliferation-inhibiting effect of metformin exposure was regulated by decreasing adenosine triphosphate level and respiratory enzyme activity in the mitochondria; this process was possibly mediated by the adenosine monophosphate-activated protein kinase (AMPK)/tuberous sclerosis complex 2 (TSC2)/mammalian target of rapamycin (mTOR) signaling pathway, which was regulated by the down-expressed miR-1764 and by the decreased antioxidant enzyme activity and excessive reactive oxygen species generation. Metformin 38-47 mechanistic target of rapamycin kinase Homo sapiens 332-336 34481229-8 2021 Our findings suggest appropriate dose of exogenous 17beta-estradiol treatment can ameliorate the inhibitory effect of metformin on SC proliferation via the regulation of AMPK/TSC2/mTOR signaling pathway, this might reduce the risk of poor male fertility caused by the abuse of anti-diabetic agents. Metformin 118-127 mechanistic target of rapamycin kinase Homo sapiens 180-184 34479029-2 2021 The anti-diabetic agent metformin (MET) and the aspirin metabolite salicylate (SAL) are shown to activate AMP-activated protein kinase (AMPK), suppress de novo lipogenesis (DNL), the mammalian target of rapamycin (mTOR) pathway and reduce PrCa proliferation in-vitro. Metformin 24-33 mechanistic target of rapamycin kinase Homo sapiens 183-212 34479029-2 2021 The anti-diabetic agent metformin (MET) and the aspirin metabolite salicylate (SAL) are shown to activate AMP-activated protein kinase (AMPK), suppress de novo lipogenesis (DNL), the mammalian target of rapamycin (mTOR) pathway and reduce PrCa proliferation in-vitro. Metformin 24-33 mechanistic target of rapamycin kinase Homo sapiens 214-218 34745769-6 2021 Mechanistically, metformin induced activation of the JAK1/2/3/STAT5 and AKT/mTOR pathways in a p38 MAPK-dependent manner rather than an AMPK-dependent manner. Metformin 17-26 mechanistic target of rapamycin kinase Homo sapiens 76-80 34351835-4 2021 Drugs targeting mTOR and AMPK, such as sirolimus, rapamycin, and metformin, have shown some efficacy and tolerability in clinical trials on patients with SLE, but have not led to breakthroughs. Metformin 65-74 mechanistic target of rapamycin kinase Homo sapiens 16-20 34486387-8 2021 While 0.1mM/L metformin upregulated the expression of BECLIN1 and LC3 I/II gene and inhibited the expression of mTOR and GSK3beta, contribute to reverse the osteogenesis inhibition of ASCs caused by high glucose. Metformin 14-23 mechanistic target of rapamycin kinase Homo sapiens 112-116 34690930-8 2021 However, Metformin, as a first-line medicine for the treatment of type 2 diabetes mellitus (T2DM), may be a potential drug benefiting diabetic patients with SARS-CoV-2 infection, probably via a suppression of mTOR signaling together with its anti-inflammatory and anti-fibrosis function in lung. Metformin 9-18 mechanistic target of rapamycin kinase Homo sapiens 209-213 34296521-7 2021 Additionally, we found that metformin suppressed HLE-B3 cell senescence by improving lysosomal function and inactivating mTOR. Metformin 28-37 mechanistic target of rapamycin kinase Homo sapiens 121-125 34576192-11 2021 Metformin and DCA inhibited mTOR complex I signaling through upregulated AMPK-independent REDD1. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 28-32 34255745-0 2021 Inhibition of mTOR signaling and clinical activity of metformin in oral premalignant lesions. Metformin 54-63 mechanistic target of rapamycin kinase Homo sapiens 14-18 34255745-2 2021 Here, we conducted a single-arm, open label phase IIa clinical trial (NCT02581137) in individuals with oral premalignant lesions (OPL) to explore the potential of metformin to target PI3K/mTOR signaling for HNSCC prevention. Metformin 163-172 mechanistic target of rapamycin kinase Homo sapiens 188-192 34255745-11 2021 CONCLUSIONS: This is the first phase II trial of metformin in individuals with OPL, providing evidence that metformin administration results in encouraging histological responses and mTOR pathway modulation, thus supporting its further investigation as a chemopreventive agent. Metformin 49-58 mechanistic target of rapamycin kinase Homo sapiens 183-187 34255745-11 2021 CONCLUSIONS: This is the first phase II trial of metformin in individuals with OPL, providing evidence that metformin administration results in encouraging histological responses and mTOR pathway modulation, thus supporting its further investigation as a chemopreventive agent. Metformin 108-117 mechanistic target of rapamycin kinase Homo sapiens 183-187 34434111-0 2021 Metformin Attenuates Silica-Induced Pulmonary Fibrosis by Activating Autophagy via the AMPK-mTOR Signaling Pathway. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 92-96 34062070-0 2021 The role of AMPK/mTOR signaling pathway in anticancer activity of metformin. Metformin 66-75 mechanistic target of rapamycin kinase Homo sapiens 17-21 34440224-5 2021 Metformin exerts anti-cancer properties by activating the MAPK pathway, inhibiting the PI3K/AKT/mTOR pathway, increasing tumor suppressor genes, inducing G2/M cycle arrest, and various other processes. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 96-100 34434111-8 2021 These results suggest that metformin could inhibit silica-induced pulmonary fibrosis by activating autophagy through the AMPK-mTOR pathway. Metformin 27-36 mechanistic target of rapamycin kinase Homo sapiens 126-130 34434111-7 2021 Besides, metformin increased the expression levels of phosphorylated adenosine 5"-monophosphate (AMP)-activated protein kinase (p-AMPK), microtubule-associated protein (MAP) light chain 3B (LC3B) and Beclin1 proteins, and reduced levels of phosphorylated mammalian target of rapamycin (p-mTOR) and p62 proteins in vivo and in vitro. Metformin 9-18 mechanistic target of rapamycin kinase Homo sapiens 255-284 34434111-7 2021 Besides, metformin increased the expression levels of phosphorylated adenosine 5"-monophosphate (AMP)-activated protein kinase (p-AMPK), microtubule-associated protein (MAP) light chain 3B (LC3B) and Beclin1 proteins, and reduced levels of phosphorylated mammalian target of rapamycin (p-mTOR) and p62 proteins in vivo and in vitro. Metformin 9-18 mechanistic target of rapamycin kinase Homo sapiens 288-292 34421608-0 2021 Metformin Potentiates the Effects of Anlotinib in NSCLC via AMPK/mTOR and ROS-Mediated Signaling Pathways. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 65-69 34422646-1 2021 Objectives: Anti-diabetic biguanide drugs such as metformin may have anti-tumorigenic effects by behaving as AMPK activators and mTOR inhibitors. Metformin 50-59 mechanistic target of rapamycin kinase Homo sapiens 129-133 34421608-4 2021 Interesting, metformin also exerts broad anticancer effects through the activation of AMP-activated protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR). Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 140-169 34421608-4 2021 Interesting, metformin also exerts broad anticancer effects through the activation of AMP-activated protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR). Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 171-175 34421608-7 2021 Moreover, anlotinib combined with metformin induced apoptosis and oxidative stress, which was associated with the activation of AMPK and inhibition of mTOR. Metformin 34-43 mechanistic target of rapamycin kinase Homo sapiens 151-155 34152528-2 2021 Metformin has in-vitro anti-cancer activity, through AMPK activation and mTOR inhibition. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 73-77 34257723-8 2021 Thus, the current data suggested that metformin may have potential value as a synergistic therapy targeting both the COX-2 and mTOR signaling pathways. Metformin 38-47 mechanistic target of rapamycin kinase Homo sapiens 127-131 34218545-6 2021 In this regard, we clarify that it is valuable to consider the therapeutic effect of mTOR inhibitor drugs and metformin by its mTOR inhibition property in the treatment of COVID-19 patients. Metformin 110-119 mechanistic target of rapamycin kinase Homo sapiens 127-131 34158423-5 2022 Emerging evidence showed that metformin possesses chemopreventive effects via both direct (e.g., adenosine monophosphate-activated protein kinase activation and subsequent inhibition of the mammalian target of rapamycin pathway) and indirect (e.g., modulation of the interaction between tumor cells and their microenvironment and gut microbiota) pathways. Metformin 30-39 mechanistic target of rapamycin kinase Homo sapiens 190-219 34154617-0 2021 Correction to: Metformin ameliorates scleroderma via inhibiting Th17 cells and reducing mTOR-STAT3 signaling in skin fibroblasts. Metformin 15-24 mechanistic target of rapamycin kinase Homo sapiens 88-92 34139918-4 2022 Areas of ongoing investigation focus on metformin"s ability to activate adenosine monophosphate kinase (AMPK), in addition to its effect on Myc mRNA, monocarboxylate transporter 1 (MCT1), hypoxia-inducible factor 1 (HIF1), mammalian target of rapamycin (mTOR), and human epidermal growth factor receptor 2 (HER2). Metformin 40-49 mechanistic target of rapamycin kinase Homo sapiens 223-252 34139918-4 2022 Areas of ongoing investigation focus on metformin"s ability to activate adenosine monophosphate kinase (AMPK), in addition to its effect on Myc mRNA, monocarboxylate transporter 1 (MCT1), hypoxia-inducible factor 1 (HIF1), mammalian target of rapamycin (mTOR), and human epidermal growth factor receptor 2 (HER2). Metformin 40-49 mechanistic target of rapamycin kinase Homo sapiens 254-258 35341775-0 2022 Metformin alleviates dexamethasone-induced apoptosis by regulating autophagy via AMPK/mTOR/p70S6K in osteoblasts. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 86-90 33929389-10 2021 Following metformin treatment, p-AMPK and p-eNOS expression increased, while p-mTOR expression decreased. Metformin 10-19 mechanistic target of rapamycin kinase Homo sapiens 79-83 33929389-12 2021 In conclusion, metformin can attenuate endothelial injuries and suppress EndMT of HCMECs under hypoxic conditions, owing to its ability to activate the AMPK pathway, increase p-AMPK/t-AMPK, and inhibit mTOR. Metformin 15-24 mechanistic target of rapamycin kinase Homo sapiens 202-206 35341775-12 2022 Treatment with the autophagy inhibitor 3-methyladenine (3-MA) attenuated the effect of metformin on apoptosis, autophagy, and the AMPK/mTOR/p70S6K signaling pathway. Metformin 87-96 mechanistic target of rapamycin kinase Homo sapiens 135-139 35341775-14 2022 Furthermore, sh-AMPK transfection and the mTOR activator MHY1485 impaired metformin-mediated inhibition of osteoblast apoptosis and promotion of autophagy. Metformin 74-83 mechanistic target of rapamycin kinase Homo sapiens 42-46 35341775-15 2022 The AMPK/mTOR/p70S6K signaling pathway plays a role in metformin-mediated apoptosis suppression and autophagy promotion. Metformin 55-64 mechanistic target of rapamycin kinase Homo sapiens 9-13 35341775-16 2022 In conclusion, metformin can alleviate Dex-induced osteoblast apoptosis by inducing autophagy via the AMPK/mTOR/p70S6K pathway. Metformin 15-24 mechanistic target of rapamycin kinase Homo sapiens 107-111 35528246-7 2022 The effects of p-cymene and metformin were studied on levels of glucose (Glu), lipid profile, liver enzymes, oxidative stress, and the expression of Akt, phospho-Akt, and mTOR (mammalian target of rapamycin) proteins, using biochemical, histological, and immunohistochemical analysis. Metformin 28-37 mechanistic target of rapamycin kinase Homo sapiens 171-175 35610639-0 2022 Metformin exerts an antitumor effect by inhibiting bladder cancer cell migration and growth, and promoting apoptosis through the PI3K/AKT/mTOR pathway. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 138-142 35610639-10 2022 Compared with that in the control group, the level of cleaved-caspase 3 and cleaved-PARP protein in the metformin group was increased in each treatment group, and the levels of p-mTOR, p-AKT, and p-PI3K decreased significantly compared with those in the control group (P < 0.05). Metformin 104-113 mechanistic target of rapamycin kinase Homo sapiens 179-183 35528246-7 2022 The effects of p-cymene and metformin were studied on levels of glucose (Glu), lipid profile, liver enzymes, oxidative stress, and the expression of Akt, phospho-Akt, and mTOR (mammalian target of rapamycin) proteins, using biochemical, histological, and immunohistochemical analysis. Metformin 28-37 mechanistic target of rapamycin kinase Homo sapiens 177-206 35434034-9 2022 Metformin had no significant effect on MCF-7R cells with lncRNA GAS5 knockdown but contrarily activated p-mTOR. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 106-110 35625721-9 2022 These findings demonstrate an association between damage of the cardiac contractile unit-desmin and sarcomere-and the iNOS/mTOR/TIMP-1/collagen axis of fibrosis in T2DM-induced cardiomyopathy, with metformin exhibiting beneficial cardiovascular pleiotropic effects. Metformin 198-207 mechanistic target of rapamycin kinase Homo sapiens 123-127 35433698-7 2022 Furthermore, the biguanide diabetes drug metformin, treatment with which enhances autophagy via AMPK-mediated mTOR inactivation, has been reported to reduce the risk of EC. Metformin 41-50 mechanistic target of rapamycin kinase Homo sapiens 110-114 35326689-0 2022 In Vivo and In Vitro Enhanced Tumoricidal Effects of Metformin, Active Vitamin D3, and 5-Fluorouracil Triple Therapy against Colon Cancer by Modulating the PI3K/Akt/PTEN/mTOR Network. Metformin 53-62 mechanistic target of rapamycin kinase Homo sapiens 170-174 35434034-0 2022 Metformin reverses tamoxifen resistance through the lncRNA GAS5-medicated mTOR pathway in breast cancer. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 74-78 35434034-10 2022 Conclusions: Metformin can inhibit overactivation of the mTOR signaling pathway through upregulating lncRNA GAS5 expression, thereby inhibiting the growth and inducing the apoptosis of BC cells, providing a new clinical treatment for BC. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 57-61 34380878-9 2022 The study also revealed that cognition-enhancing effects of metformin in aged animals were associated with the activation of the energy regulator adenosine monophosphate-activated protein kinase, diminished neuroinflammation, inhibition of the mammalian target of rapamycin signaling, and augmented autophagy in the hippocampus. Metformin 60-69 mechanistic target of rapamycin kinase Homo sapiens 244-273 35158846-5 2022 The pleiotropic effects of metformin are mainly exerted through the activation of AMP-activated protein kinase, which is the key cellular energy homeostasis regulator that inhibits mTOR, a major autophagy suppressor. Metformin 27-36 mechanistic target of rapamycin kinase Homo sapiens 181-185 35196199-11 2022 Our study shows that treatments targeting pathways to enhance autophagy have the potential for treating early AMD and provide support for the use of metformin, which has been found to reduce the risk of AMD development in human patients.Abbreviations:AMD: age-related macular degeneration; AMPK: 5" adenosine monophosphate-activated protein kinase APOE: apolipoprotein E; ATM: ataxia telangiectasia mutated; BCL2L1/Bcl-xL: BCL2-like 1; DAPI: 4"-6-diamidino-2-phenylindole; ERG: electroretinogram; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; IS/OS: inner and outer photoreceptor segments; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; OCT: optical coherence tomography; ONL: outer nuclear layer; OPs: oscillatory potentials; p-EIF4EBP1: phosphorylated eukaryotic translation initiation factor 4E binding protein 1; p-MAPK14/p38: phosphorylated mitogen-activated protein kinase 14; RPE: retinal pigment epithelium; RPS6KB/p70 S6 kinase: ribosomal protein S6 kinase; SQSTM1/p62: sequestosome 1; TP53/TRP53/p53: tumor related protein 53; TSC2: TSC complex subunit 2; WT: wild type. Metformin 149-158 mechanistic target of rapamycin kinase Homo sapiens 788-792 34004440-0 2021 Metformin prevents BAFF activation of Erk1/2 from B-cell proliferation and survival by impeding mTOR-PTEN/Akt signaling pathway. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 96-100 35072253-4 2022 The mechanism of the antitumor action of metformin is pleiotropic and involves several signalling pathways, including AMPK/mTOR (mitogen activated protein kinase/mammalian target rapamycin), STAT3 (signal transducer and activator of transcription) and numerous factors: NF-KB (nuclear factor kappa), HIF-1 alpha (hypoxia inducible factor 1), IGF-1 (insulin-like growth factor-1), which affect cell proliferation and apoptosis. Metformin 41-50 mechanistic target of rapamycin kinase Homo sapiens 123-127 33850553-0 2021 Metformin prevents PFKFB3-related aerobic glycolysis from enhancing collagen synthesis in lung fibroblasts by regulating AMPK/mTOR pathway. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 126-130 33850553-11 2021 However, this inhibitory role of metformin on PFKFB3-meditaed aerobic glycolysis and collagen synthesis was prevented by treatments with 3BDO and compound C, which are specific mTOR activator and AMPK inhibitor, respectively. Metformin 33-42 mechanistic target of rapamycin kinase Homo sapiens 177-181 33850553-12 2021 Taken together, the findings from this study suggested that metformin may prevent PFKFB3-associated aerobic glycolysis from enhancing collagen synthesis in lung fibroblasts via regulating the AMPK/mTOR pathway. Metformin 60-69 mechanistic target of rapamycin kinase Homo sapiens 197-201 34004440-7 2021 Furthermore, we noticed that metformin hindered hsBAFF-activated mTOR pathway in B cells. Metformin 29-38 mechanistic target of rapamycin kinase Homo sapiens 65-69 34004440-8 2021 Inhibition of mTOR with rapamycin or knockdown of mTOR enhanced metformin"s suppression of hsBAFF-induced phosphorylation of S6K1, PTEN, Akt, and Erk1/2, as well as B-cell proliferation/viability. Metformin 64-73 mechanistic target of rapamycin kinase Homo sapiens 14-18 34004440-8 2021 Inhibition of mTOR with rapamycin or knockdown of mTOR enhanced metformin"s suppression of hsBAFF-induced phosphorylation of S6K1, PTEN, Akt, and Erk1/2, as well as B-cell proliferation/viability. Metformin 64-73 mechanistic target of rapamycin kinase Homo sapiens 50-54 34004440-9 2021 These results indicate that metformin prevents BAFF activation of Erk1/2 from cell proliferation and survival by impeding mTOR-PTEN/Akt signaling pathway in normal and neoplastic B-lymphoid cells. Metformin 28-37 mechanistic target of rapamycin kinase Homo sapiens 122-126 34714980-3 2022 Our previous study showed that metformin protected against the pathophysiology of AAA by reducing the activation of the PI3K/AKT/mTOR pathway. Metformin 31-40 mechanistic target of rapamycin kinase Homo sapiens 129-133 33838541-4 2021 The use of metformin for chemoprevention has been shown to reduce CRC and adenoma incidence through the upregulation of AMPK, which causes cell cycle arrest in the Gap 1-S (G1-S) phase and inhibits the mTOR pathway, even potentially reversing the epithelial-mesenchymal transition. Metformin 11-20 mechanistic target of rapamycin kinase Homo sapiens 202-206 33850550-10 2021 These findings suggested that metformin may reduce DN damage via regulation of the AMPK-mTOR-autophagy axis and indicated that metformin may be considered as a potential target in the treatment of DN. Metformin 30-39 mechanistic target of rapamycin kinase Homo sapiens 88-92 33850550-10 2021 These findings suggested that metformin may reduce DN damage via regulation of the AMPK-mTOR-autophagy axis and indicated that metformin may be considered as a potential target in the treatment of DN. Metformin 127-136 mechanistic target of rapamycin kinase Homo sapiens 88-92 33524789-6 2021 First, many studies showed that metformin could induce autophagy via a number of signaling pathways, including AMPK-related signaling pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3beta, and TRIB3. Metformin 32-41 mechanistic target of rapamycin kinase Homo sapiens 154-158 33689478-4 2021 Commonly accepted mechanisms of metformin action include AMPK activation and inhibition of mTOR pathways, which are evaluated in multiple diseases. Metformin 32-41 mechanistic target of rapamycin kinase Homo sapiens 91-95 33524789-6 2021 First, many studies showed that metformin could induce autophagy via a number of signaling pathways, including AMPK-related signaling pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3beta, and TRIB3. Metformin 32-41 mechanistic target of rapamycin kinase Homo sapiens 218-222 33524789-8 2021 Thirdly, two types of signaling pathways including PI3K/AKT/mTOR and endoplasmic reticulum (ER) stress could bidirectionally impact the effectiveness of metformin on autophagy. Metformin 153-162 mechanistic target of rapamycin kinase Homo sapiens 60-64 33690729-7 2021 Direct anti-cancer effects of metformin target signaling pathways that are involved in cellular growth and proliferation, e.g. the AKT/PKB/mTOR pathway. Metformin 30-39 mechanistic target of rapamycin kinase Homo sapiens 139-143 33509804-10 2021 Colon polyps removed from the metformin-treated patients showed significantly lower mTOR signal (p-S6) expression than those from patients in the placebo arm. Metformin 30-39 mechanistic target of rapamycin kinase Homo sapiens 84-88 33886150-9 2021 Moreover, cotreating the cells with metformin (30 mM) and pitavastatin (10 muM) could preserve mitochondrial function, activate AMPK, and inhibit PI3K/mTOR than treatment with metformin or pitavastatin alone. Metformin 36-45 mechanistic target of rapamycin kinase Homo sapiens 151-155 33886150-10 2021 These findings clearly indicated that metformin plus pitavastatin had a synergistic anticancer effect on pancreatic cancer cells, potentially caused due to the activation of AMPK and inhibition of PI3K/mTOR signaling. Metformin 38-47 mechanistic target of rapamycin kinase Homo sapiens 202-206 33439105-8 2021 Metformin increased the phosphorylation of AMPK and decreased the phosphorylation of mammalian target of rapamycin and extracellular signal-regulated kinase and the expression of cystic fibrosis transmembrane conductance regulator, aquaporin I, transforming growth factor-beta and type 1 collagen in the liver. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 85-114 33141412-7 2021 Surprisingly, our results demonstrated that the treatment in which we applied the combination of quercetin and metformin significantly reversed these changes and had a pronounced effect on the endometrial implant size and gene expression levels of mTOR and autophagy markers in ectopic endometrium. Metformin 111-120 mechanistic target of rapamycin kinase Homo sapiens 248-252 33650651-0 2021 Metformin inhibits mTOR and c-Myc by decreasing YAP protein expression in OSCC cells. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 19-23 33650651-9 2021 In addition, compared to the control treatment, metformin treatment decreased the protein levels of YAP, mTOR, p-mTOR and c-Myc. Metformin 48-57 mechanistic target of rapamycin kinase Homo sapiens 105-109 33650651-9 2021 In addition, compared to the control treatment, metformin treatment decreased the protein levels of YAP, mTOR, p-mTOR and c-Myc. Metformin 48-57 mechanistic target of rapamycin kinase Homo sapiens 113-117 33650651-10 2021 The overexpression of YAP alleviated the inhibitory effect of metformin on the protein expression of mTOR, p-mTOR and c-Myc. Metformin 62-71 mechanistic target of rapamycin kinase Homo sapiens 101-105 33650651-10 2021 The overexpression of YAP alleviated the inhibitory effect of metformin on the protein expression of mTOR, p-mTOR and c-Myc. Metformin 62-71 mechanistic target of rapamycin kinase Homo sapiens 109-113 33650651-11 2021 The combination of metformin and verteporfin markedly enhanced the effects of metformin on the protein expression of mTOR, p-mTOR and c-Myc. Metformin 19-28 mechanistic target of rapamycin kinase Homo sapiens 117-121 33650651-11 2021 The combination of metformin and verteporfin markedly enhanced the effects of metformin on the protein expression of mTOR, p-mTOR and c-Myc. Metformin 19-28 mechanistic target of rapamycin kinase Homo sapiens 125-129 33650651-11 2021 The combination of metformin and verteporfin markedly enhanced the effects of metformin on the protein expression of mTOR, p-mTOR and c-Myc. Metformin 78-87 mechanistic target of rapamycin kinase Homo sapiens 117-121 33650651-11 2021 The combination of metformin and verteporfin markedly enhanced the effects of metformin on the protein expression of mTOR, p-mTOR and c-Myc. Metformin 78-87 mechanistic target of rapamycin kinase Homo sapiens 125-129 33650651-12 2021 Therefore, the results of the present study suggest that metformin suppresses OSCC by inhibiting YAP protein expression and by suppressing the YAP-mediated effects of metformin on the protein expression of mTOR and c-Myc. Metformin 57-66 mechanistic target of rapamycin kinase Homo sapiens 206-210 33650651-12 2021 Therefore, the results of the present study suggest that metformin suppresses OSCC by inhibiting YAP protein expression and by suppressing the YAP-mediated effects of metformin on the protein expression of mTOR and c-Myc. Metformin 167-176 mechanistic target of rapamycin kinase Homo sapiens 206-210 33443781-10 2021 Additional analysis demonstrated that metformin treatment in late middle age increased adenosine monophosphate-activated protein kinase activation, reduced proinflammatory cytokine levels, and the mammalian target of rapamycin signaling, and enhanced autophagy in the hippocampus. Metformin 38-47 mechanistic target of rapamycin kinase Homo sapiens 197-226 33652909-9 2021 In addition, metformin activated the pathways of AMPKalpha and MEK/ERK to phosphorylate p27(Thr198) and reduce mTOR phosphorylation in cells. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 111-115 33161784-4 2021 Areas covered: The authors review literature on metformin treatment in Parkinson"s disease, Huntington"s disease and other neurological diseases of the CNS along with neuroprotective effects of AMPK activation and suppression of the mammalian target of rapamycin (mTOR) pathway on peripheral neuropathy and neuropathic pain. Metformin 48-57 mechanistic target of rapamycin kinase Homo sapiens 264-268 33148437-6 2021 However, studies have shown that metformin is also able to target several other ageing pathways, thereby inhibiting mammalian target of rapamycin (mTOR), increasing AMPK activity and improving DNA repair. Metformin 33-42 mechanistic target of rapamycin kinase Homo sapiens 116-145 33148437-6 2021 However, studies have shown that metformin is also able to target several other ageing pathways, thereby inhibiting mammalian target of rapamycin (mTOR), increasing AMPK activity and improving DNA repair. Metformin 33-42 mechanistic target of rapamycin kinase Homo sapiens 147-151 32951587-5 2021 In this review, we summarize the chemosensitization effects of metformin and focus primarily on its molecular mechanisms in enhancing the sensitivity of multiple chemotherapeutic drugs, through targeting of mTOR, ERK/P70S6K, NF-kappaB/HIF-1alpha, and mitogenactivated protein kinase (MAPK) signaling pathways, as well as by down-regulating the expression of CSC genes and pyruvate kinase isoenzyme M2 (PKM2). Metformin 63-72 mechanistic target of rapamycin kinase Homo sapiens 207-211 33007330-8 2021 Combination of NT157 with metformin induced enhanced inhibition of p-IGF1R, p-ERK1/2 and p-mTOR. Metformin 26-35 mechanistic target of rapamycin kinase Homo sapiens 91-95 33365058-0 2021 Metformin alleviates beta-glycerophosphate-induced calcification of vascular smooth muscle cells via AMPK/mTOR-activated autophagy. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 106-110 33365058-6 2021 Metformin increased the number of autophagosomes, green fluorescent LC3 puncta and the levels of LC3II/I, beclin 1, alpha-SMA and phosphorylated (p)-AMPK in the VSMCs that were treated with beta-glycerophosphate when compared to controls; whereas, calcium deposition and the expression levels of RUNX2 and p-mTOR were found to be decreased. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 308-312 33365058-8 2021 The results of the present study suggested that metformin may alleviate beta-glycerophosphate-induced calcification of VSMCs, which may be attributed to the activation of AMPK/mTOR signaling pathway-dependent autophagy. Metformin 48-57 mechanistic target of rapamycin kinase Homo sapiens 176-180 32994182-5 2021 In cultured mouse mammary and human breast cancer cells, metformin suppressed DPP-4 inhibitor KR62436 (KR)-induced EMT and cell migration via suppression of the mTOR pathway associated with AMPK activation. Metformin 57-66 mechanistic target of rapamycin kinase Homo sapiens 161-165 33232684-1 2021 OBJECTIVES: The COVID-19 pandemic presents an urgent need to investigate whether existing drugs can enhance or even worsen prognosis; metformin, a known mammalian target of rapamycin (m-TOR) inhibitor, has been identified as a potential agent. Metformin 134-143 mechanistic target of rapamycin kinase Homo sapiens 153-182 33232684-11 2021 These findings suggest a relative survival benefit in nursing home residents on metformin, potentially through its mTOR inhibition effects. Metformin 80-89 mechanistic target of rapamycin kinase Homo sapiens 115-119 32994182-3 2021 Metformin has been shown to inhibit the mTOR signaling pathway. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 40-44 32994182-4 2021 In this study, we investigated whether metformin mitigates breast cancer metastasis induced by a DPP-4 inhibitor via suppression of mTOR signaling. Metformin 39-48 mechanistic target of rapamycin kinase Homo sapiens 132-136 32861747-5 2020 Transfection of mir-181c, one of the positive regulators of Akt and mTOR, lead to an increase in the cell resistance to both mTOR inhibitors, rapamycin, and metformin, which correlated with Raptor overexpression and activation of Akt/AP-1 signaling. Metformin 157-166 mechanistic target of rapamycin kinase Homo sapiens 68-72 33262823-0 2021 Metformin inhibits epithelial-mesenchymal transition of oral squamous cell carcinoma via the mTOR/HIF-1alpha/PKM2/STAT3 pathway. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 93-97 33262823-9 2021 Moreover, metformin reversed EMT in OSCC by inhibiting the mTOR-associated HIF-1alpha/PKM2/STAT3 signaling pathway. Metformin 10-19 mechanistic target of rapamycin kinase Homo sapiens 59-63 33575476-0 2021 Metformin enhances anti-cancer effects of cisplatin in meningioma through AMPK-mTOR signaling pathways. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 79-83 33575476-5 2021 Additionally, metformin activated adenosine monophosphate activated protein kinase (AMPK) and repressed the mammalian target of rapamycin (mTOR) signaling pathways via an AMPK-dependent mechanism. Metformin 14-23 mechanistic target of rapamycin kinase Homo sapiens 108-137 33575476-5 2021 Additionally, metformin activated adenosine monophosphate activated protein kinase (AMPK) and repressed the mammalian target of rapamycin (mTOR) signaling pathways via an AMPK-dependent mechanism. Metformin 14-23 mechanistic target of rapamycin kinase Homo sapiens 139-143 33575476-8 2021 These results demonstrate metformin enhanced the anti-cancer effect of cisplatin in meningioma in vitro and in vivo, an effect mediated through the activation of AMPK and repression of mTOR signaling pathways. Metformin 26-35 mechanistic target of rapamycin kinase Homo sapiens 185-189 32934724-4 2020 The direct mechanisms of metformin include inhibition of the LKB1-AMP-activated protein kinase-mTOR, PI3K-Akt and insulin-like growth factor 1-related signaling pathways, which reduces the proliferation and promotes the apoptosis of EC cells. Metformin 25-34 mechanistic target of rapamycin kinase Homo sapiens 95-99 32657143-8 2021 In the metformin treated group, the expression of Bax and PUMA genes was enhanced while the expression of Bcl-2, hTERT, mTOR, and p53 genes declined. Metformin 7-16 mechanistic target of rapamycin kinase Homo sapiens 120-124 33116117-8 2020 Metformin significantly modulated the profiles of the SASP elicited by LY2835219 by inhibiting the mTOR and stat3 pathways. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 99-103 32825760-4 2020 Among the latter, the antidiabetic drug metformin exerts antitumor activity via the activation of AMPK and the subsequent inhibition of mTOR signaling. Metformin 40-49 mechanistic target of rapamycin kinase Homo sapiens 136-140 32943543-7 2020 Addition of metformin following ADT induced apoptosis, attenuated mTOR activation by ADT, reduced senescent cell number in vitro and inhibited tumor growth in PC PDX models. Metformin 12-21 mechanistic target of rapamycin kinase Homo sapiens 66-70 32911743-11 2020 Metformin treatment increased p-AMPK and decreased mTOR (pS6) expression; these effects were reversed by addition of mevalonate. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 51-55 32589349-0 2020 Effects of metformin and pioglitazone combination on apoptosis and AMPK/mTOR signaling pathway in human anaplastic thyroid cancer cells. Metformin 11-20 mechanistic target of rapamycin kinase Homo sapiens 72-76 32945402-0 2020 Metformin promotes cell proliferation and osteogenesis under high glucose condition by regulating the ROS-AKT-mTOR axis. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 110-114 32945402-8 2020 Furthermore, metformin significantly scavenged reactive oxygen species (ROS) induced by high glucose levels, and regulated the ROS-AKT-mTOR axis inhibited by high glucose levels, suggesting the protective effects of metformin against high glucose levels via regulation of the ROS-AKT-mTOR axis. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 135-139 32945402-8 2020 Furthermore, metformin significantly scavenged reactive oxygen species (ROS) induced by high glucose levels, and regulated the ROS-AKT-mTOR axis inhibited by high glucose levels, suggesting the protective effects of metformin against high glucose levels via regulation of the ROS-AKT-mTOR axis. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 284-288 32945402-8 2020 Furthermore, metformin significantly scavenged reactive oxygen species (ROS) induced by high glucose levels, and regulated the ROS-AKT-mTOR axis inhibited by high glucose levels, suggesting the protective effects of metformin against high glucose levels via regulation of the ROS-AKT-mTOR axis. Metformin 216-225 mechanistic target of rapamycin kinase Homo sapiens 135-139 32945402-8 2020 Furthermore, metformin significantly scavenged reactive oxygen species (ROS) induced by high glucose levels, and regulated the ROS-AKT-mTOR axis inhibited by high glucose levels, suggesting the protective effects of metformin against high glucose levels via regulation of the ROS-AKT-mTOR axis. Metformin 216-225 mechanistic target of rapamycin kinase Homo sapiens 284-288 32825834-7 2020 The Cancer Genome Atlas dataset, an L1000 microarray with Gene Set Enrichment Analysis (GSEA) analysis, Western blot analysis and an animal model were used to study the activity of the AKT/mTOR pathway in response to the synergistic effects of neoadjuvant metformin combined with chemotherapy. Metformin 256-265 mechanistic target of rapamycin kinase Homo sapiens 189-193 32825834-9 2020 The protein profile induced by low- concentration metformin in ovarian cancer predominantly involved the AKT/mTOR pathway. Metformin 50-59 mechanistic target of rapamycin kinase Homo sapiens 109-113 32825760-6 2020 We have demonstrated metformin"s ability to enhance the cytostatic activity of the tamoxifen and rapamycin on both parent MCF-7 cells and MCF-7-resistant derivates mediated via the suppression of mTOR signaling and growth-related transcriptional factors. Metformin 21-30 mechanistic target of rapamycin kinase Homo sapiens 196-200 32765083-0 2020 Metformin Induces Autophagy via the AMPK-mTOR Signaling Pathway in Human Hepatocellular Carcinoma Cells. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 41-45 32470453-8 2020 As a plausible mechanism to mediate T-cell function, metformin showed enhanced potential to regulate mechanistic targets of rapamycin (mTOR), STAT5 and adenosine-monophosphate-activated protein kinase (AMPK) signalling pathways. Metformin 53-62 mechanistic target of rapamycin kinase Homo sapiens 101-133 32470453-8 2020 As a plausible mechanism to mediate T-cell function, metformin showed enhanced potential to regulate mechanistic targets of rapamycin (mTOR), STAT5 and adenosine-monophosphate-activated protein kinase (AMPK) signalling pathways. Metformin 53-62 mechanistic target of rapamycin kinase Homo sapiens 135-139 32748870-3 2020 In this context, the antidiabetic drug metformin is able to inhibit mTOR, providing a rationale for the use of metformin and everolimus in combination. Metformin 39-48 mechanistic target of rapamycin kinase Homo sapiens 68-72 32748870-3 2020 In this context, the antidiabetic drug metformin is able to inhibit mTOR, providing a rationale for the use of metformin and everolimus in combination. Metformin 111-120 mechanistic target of rapamycin kinase Homo sapiens 68-72 32748870-8 2020 Using everolimus-resistant NET cells, we confirmed that metformin maintained its effects, acting by two different pathways: Akt-dependent or independent, depending on the cell type, with both leading to mTOR suppression. Metformin 56-65 mechanistic target of rapamycin kinase Homo sapiens 203-207 32765083-2 2020 Our study was designed to determine the effect of metformin on the cell autophagy and autophagic flux via the AMPK-mTOR signaling pathway in human hepatocellular carcinoma (HCC) cells. Metformin 50-59 mechanistic target of rapamycin kinase Homo sapiens 115-119 32765083-8 2020 In metformin-induced autophagy, AMPK expression was activated, and the phosphorylation levels of mTOR and p70 S6 Kinase were inhibited. Metformin 3-12 mechanistic target of rapamycin kinase Homo sapiens 97-101 32765083-11 2020 Conclusion: Metformin could induce the autophagy, autophagic flux, and activate the AMPK-mTOR signaling pathway in human HCC cells. Metformin 12-21 mechanistic target of rapamycin kinase Homo sapiens 89-93 33099954-1 2020 PURPOSE: To investigate the influences of metformin on the proliferation and apoptosis of mouse melanoma B16 cells through regulating the phosphatidylinositol 3-hydroxy kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. Metformin 42-51 mechanistic target of rapamycin kinase Homo sapiens 206-235 32229782-17 2020 Metformin exerted strong PI3K/Akt/mTOR pathway inactivation effects after 24-hour exposure (increasing pAMPK p<0.01, decreasing pAkt, p<0.01; and pS6, p<0.05). Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 34-38 33099954-1 2020 PURPOSE: To investigate the influences of metformin on the proliferation and apoptosis of mouse melanoma B16 cells through regulating the phosphatidylinositol 3-hydroxy kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. Metformin 42-51 mechanistic target of rapamycin kinase Homo sapiens 237-241 32734128-2 2020 In NSCLC cells, metformin suppresses PI3K/AKT/mTOR signaling pathway, but effect of metformin on RAS/ RAF/MEK/ERK signaling pathway is controversial; several studies showed the inhibition of ERK activity, while others demonstrated the activation of ERK in response to metformin exposure. Metformin 16-25 mechanistic target of rapamycin kinase Homo sapiens 46-50 32460059-1 2020 Metformin is an anti-diabetic drug known to have anticancer activity by inhibiting mechanistic target of rapamycin (mTOR); however, other molecular mechanisms may also be involved. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 83-114 32460059-1 2020 Metformin is an anti-diabetic drug known to have anticancer activity by inhibiting mechanistic target of rapamycin (mTOR); however, other molecular mechanisms may also be involved. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 116-120 32460059-6 2020 Thus, metformin has a clinical potential for patients with leukemia cells positive for AXL and the other TAM proteins as well as activated mTOR. Metformin 6-15 mechanistic target of rapamycin kinase Homo sapiens 139-143 32627027-12 2020 Exposure of the cells to TGF-beta1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF-beta1-induced-EMT through the down-regulation of the Smad pathway in PANC-1 cells and the downregulation of the Akt/mTOR pathway in BxPC-3 cells. Metformin 145-154 mechanistic target of rapamycin kinase Homo sapiens 65-94 32627027-12 2020 Exposure of the cells to TGF-beta1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF-beta1-induced-EMT through the down-regulation of the Smad pathway in PANC-1 cells and the downregulation of the Akt/mTOR pathway in BxPC-3 cells. Metformin 145-154 mechanistic target of rapamycin kinase Homo sapiens 96-100 32627027-12 2020 Exposure of the cells to TGF-beta1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF-beta1-induced-EMT through the down-regulation of the Smad pathway in PANC-1 cells and the downregulation of the Akt/mTOR pathway in BxPC-3 cells. Metformin 145-154 mechanistic target of rapamycin kinase Homo sapiens 311-315 32627027-12 2020 Exposure of the cells to TGF-beta1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF-beta1-induced-EMT through the down-regulation of the Smad pathway in PANC-1 cells and the downregulation of the Akt/mTOR pathway in BxPC-3 cells. Metformin 172-181 mechanistic target of rapamycin kinase Homo sapiens 65-94 32627027-12 2020 Exposure of the cells to TGF-beta1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF-beta1-induced-EMT through the down-regulation of the Smad pathway in PANC-1 cells and the downregulation of the Akt/mTOR pathway in BxPC-3 cells. Metformin 172-181 mechanistic target of rapamycin kinase Homo sapiens 96-100 32627027-12 2020 Exposure of the cells to TGF-beta1 activated the Smad2/3 and Akt/mammalian target of rapamycin (mTOR) pathways, and this effect was inhibited by metformin, suggesting that metformin inhibits TGF-beta1-induced-EMT through the down-regulation of the Smad pathway in PANC-1 cells and the downregulation of the Akt/mTOR pathway in BxPC-3 cells. Metformin 172-181 mechanistic target of rapamycin kinase Homo sapiens 311-315 32627027-14 2020 On the whole, the findings of the present study suggest that metformin inhibits EMT and cancer metastasis through the Smad or Akt/mTOR pathway. Metformin 61-70 mechanistic target of rapamycin kinase Homo sapiens 130-134 32734128-3 2020 Metformin-induced activation of ERK is therapeutically important, since metformin could enhance cell proliferation through RAS/RAF/MEK/ERK pathway and lead to impairment of its anticancer activity suppressing PI3K/AKT/mTOR pathway, requiring blockade of both signaling pathways for more efficient antitumor effect. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 218-222 32734128-3 2020 Metformin-induced activation of ERK is therapeutically important, since metformin could enhance cell proliferation through RAS/RAF/MEK/ERK pathway and lead to impairment of its anticancer activity suppressing PI3K/AKT/mTOR pathway, requiring blockade of both signaling pathways for more efficient antitumor effect. Metformin 72-81 mechanistic target of rapamycin kinase Homo sapiens 218-222 32734128-5 2020 We show that metformin alone blocks PI3K/AKT/mTOR signaling pathway but induces the activation and phosphorylation of ERK. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 45-49 32251713-6 2020 AIP silencing abolished the reduction of mTOR phosphorylation induced by metformin and octreotide. Metformin 73-82 mechanistic target of rapamycin kinase Homo sapiens 41-45 32048246-0 2020 Metformin accelerates myelin recovery and ameliorates behavioral deficits in the animal model of multiple sclerosis via adjustment of AMPK/Nrf2/mTOR signaling and maintenance of endogenous oligodendrogenesis during brain self-repairing period. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 144-148 32048246-4 2020 RESULTS: MET remarkably increased the localization of precursor OLGs (NG2+/O4+ cells) and subsequently the renewal of mature OLGs (MOG+ cells) in the corpus callosum via AMPK/mammalian target of rapamycin (mTOR) pathway. Metformin 9-12 mechanistic target of rapamycin kinase Homo sapiens 175-204 32048246-9 2020 CONCLUSIONS: Altogether, our study reveals that MET effectively induces lesion reduction and elevated molecular processes that support myelin recovery via direct activation of AMPK and indirect regulation of AMPK/Nrf2/mTOR pathway in OLGs. Metformin 48-51 mechanistic target of rapamycin kinase Homo sapiens 218-222 32048246-4 2020 RESULTS: MET remarkably increased the localization of precursor OLGs (NG2+/O4+ cells) and subsequently the renewal of mature OLGs (MOG+ cells) in the corpus callosum via AMPK/mammalian target of rapamycin (mTOR) pathway. Metformin 9-12 mechanistic target of rapamycin kinase Homo sapiens 206-210 32547075-7 2020 Western blotting, cell proliferation, cell migration and invasion were used to verify that metformin enhances autophagy in GC cells through the AMPK-mTOR signalling pathway. Metformin 91-100 mechanistic target of rapamycin kinase Homo sapiens 149-153 32547075-13 2020 Furthermore, we verified that metformin can upregulate beclin1-mediated autophagy to inhibit GC cells through the AMPK-mTOR signalling pathway. Metformin 30-39 mechanistic target of rapamycin kinase Homo sapiens 119-123 32495867-0 2020 Metformin reduces pancreatic cancer cell proliferation and increases apoptosis through MTOR signaling pathway and its dose-effect relationship. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 87-91 32443566-2 2020 The current consensus is that metformin exerts indirect pleiotropy on core metabolic hallmarks of aging, such as the insulin/insulin-like growth factor 1 and AMP-activated protein kinase/mammalian Target Of Rapamycin signaling pathways, downstream of its primary inhibitory effect on mitochondrial respiratory complex I. Alternatively, but not mutually exclusive, metformin can exert regulatory effects on components of the biologic machinery of aging itself such as chromatin-modifying enzymes. Metformin 30-39 mechanistic target of rapamycin kinase Homo sapiens 187-216 32495867-10 2020 Moreover, Metformin treatment groups (0, 20, and 40 mM) had more apoptotic PANC-1 cells, higher expression levels of pro-apoptosis proteins Caspase-3 and Bax and lower expression levels of anti-apoptosis protein Bcl-2 and the mTOR pathway-related proteins PI3K, p-Akt, and p-mTOR in cells than Control group (p<0.05). Metformin 10-19 mechanistic target of rapamycin kinase Homo sapiens 226-230 32495867-10 2020 Moreover, Metformin treatment groups (0, 20, and 40 mM) had more apoptotic PANC-1 cells, higher expression levels of pro-apoptosis proteins Caspase-3 and Bax and lower expression levels of anti-apoptosis protein Bcl-2 and the mTOR pathway-related proteins PI3K, p-Akt, and p-mTOR in cells than Control group (p<0.05). Metformin 10-19 mechanistic target of rapamycin kinase Homo sapiens 275-279 32495867-11 2020 CONCLUSIONS: Metformin modulates the mTOR signaling pathway to reduce the proliferation of pancreatic cancer cell, but increase their apoptosis. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 37-41 32248762-11 2020 Metformin may exert its effects by normalizing myocardial AMPK and mammalian target-of-rapamycin activities, improving fatty acid oxidation, and reducing oxidative stress. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 67-96 31789625-9 2020 Metformin downregulated the levels of p-NF-kappaB p65, p-Erk1/2, p-AKT, and p-mTOR proteins. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 78-82 31789625-12 2020 Our discovery revealed that metformin, via increasing the expression of microRNA-7 mediated by AMPK, regulates the AKT/mTOR, MAPK/Erk, and NF-kappaB signaling pathways, thereby suppressing A549 cell growth, migration, and invasion. Metformin 28-37 mechanistic target of rapamycin kinase Homo sapiens 119-123 32099330-9 2020 Metformin and TUG1 knockdown via small interfering RNA both inhibited proliferation and migration while promoted autophagy via the AMPK/mTOR pathway in vascular wall cells. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 136-140 32183017-4 2020 We have also evaluated the ability of metformin (Metf), an antidiabetic type II compound that acts through inhibition of the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway to sensitize resistant cells to PDT. Metformin 38-47 mechanistic target of rapamycin kinase Homo sapiens 161-190 32183017-4 2020 We have also evaluated the ability of metformin (Metf), an antidiabetic type II compound that acts through inhibition of the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway to sensitize resistant cells to PDT. Metformin 38-47 mechanistic target of rapamycin kinase Homo sapiens 192-196 31874705-3 2020 Metformin is a first-line medication for treatment of type 2 diabetes which is known to activate AMPK and induce autophagy through the inhibition of mammalian target of rapamycin (mTOR1) signaling. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 149-178 32068959-2 2020 Aging-related pathways such as mTOR and AMPK, which are major targets of anti-aging interventions including rapamcyin, metformin, and exercise, either directly regulate or intersect with metabolic pathways. Metformin 119-128 mechanistic target of rapamycin kinase Homo sapiens 31-35 31926250-2 2020 Metformin, a classic hypoglycemic drug for diabetes recently delivered us a new identity that it exerted anti-tumor activity through suppressing mTOR in various tumors. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 145-149 32099330-0 2020 Metformin Activates the AMPK-mTOR Pathway by Modulating lncRNA TUG1 to Induce Autophagy and Inhibit Atherosclerosis. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 29-33 32099330-11 2020 Conclusion: Taken together, our data demonstrate that metformin might function to prevent AS by activating the AMPK/mTOR pathway via lncRNA TUG1. Metformin 54-63 mechanistic target of rapamycin kinase Homo sapiens 116-120 31570268-3 2020 The antidiabetic drug metformin inhibits both MAPK and PI3K/mTOR pathway signaling. Metformin 22-31 mechanistic target of rapamycin kinase Homo sapiens 60-64 31830378-0 2020 Combination of aloin and metformin enhances the antitumor effect by inhibiting the growth and invasion and inducing apoptosis and autophagy in hepatocellular carcinoma through PI3K/AKT/mTOR pathway. Metformin 25-34 mechanistic target of rapamycin kinase Homo sapiens 185-189 31830378-9 2020 Both the in vitro and in vivo results showed that aloin and MET alone as well as combination treatment activated the PI3K/AKT/mTOR pathway. Metformin 60-63 mechanistic target of rapamycin kinase Homo sapiens 126-130 31830378-10 2020 Overall, our research demonstrated that the concomitant treatment with aloin and MET enhances the antitumor effect by inhibiting the growth and invasion as well as inducing apoptosis and autophagy in HCC through PI3K/AKT/mTOR pathway. Metformin 81-84 mechanistic target of rapamycin kinase Homo sapiens 221-225 31607288-10 2019 PI3K/Akt/mTOR signaling pathway may be one of the molecular mechanisms of metformin on k562 cells. Metformin 74-83 mechanistic target of rapamycin kinase Homo sapiens 9-13 31902918-6 2020 Furthermore, metformin also enhanced autophagic flux, inhibited the phosphorylation of the serine/threonine protein kinase (AKT)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs) related protein levels and the level of miR-221 in LPS-stimulated RAW264.7 cells. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 129-158 31902918-6 2020 Furthermore, metformin also enhanced autophagic flux, inhibited the phosphorylation of the serine/threonine protein kinase (AKT)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs) related protein levels and the level of miR-221 in LPS-stimulated RAW264.7 cells. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 160-164 32601620-2 2020 Anti-neoplastic effects of metformin are believed through many mechanisms including activation of AMP-activated protein kinase, which controls mammalian target of rapamycin (mTOR) growth regulatory pathway. Metformin 27-36 mechanistic target of rapamycin kinase Homo sapiens 143-172 32601620-2 2020 Anti-neoplastic effects of metformin are believed through many mechanisms including activation of AMP-activated protein kinase, which controls mammalian target of rapamycin (mTOR) growth regulatory pathway. Metformin 27-36 mechanistic target of rapamycin kinase Homo sapiens 174-178 31583436-1 2019 PURPOSE: Metformin activates AMP-related pathways leading to inactivation of mammalian target of rapamycin (mTOR) and suppression of its downstream effectors, crucial for cancer growth. Metformin 9-18 mechanistic target of rapamycin kinase Homo sapiens 77-106 31583436-1 2019 PURPOSE: Metformin activates AMP-related pathways leading to inactivation of mammalian target of rapamycin (mTOR) and suppression of its downstream effectors, crucial for cancer growth. Metformin 9-18 mechanistic target of rapamycin kinase Homo sapiens 108-112 32341701-7 2020 The intervention with metformin in diabetic rats inhibited the mammalian target of rapamycin mRNA expression and caused an increase in the transcriptional activity of the Foxp3 gene in parapancreatic adipose tissue. Metformin 22-31 mechanistic target of rapamycin kinase Homo sapiens 63-92 31780804-0 2019 Full title: High glucose protects mesenchymal stem cells from metformin-induced apoptosis through the AMPK-mediated mTOR pathway. Metformin 62-71 mechanistic target of rapamycin kinase Homo sapiens 116-120 31780804-6 2019 In this study, we found that metformin induces MSC apoptosis during intensive glucose control, while high glucose (standard glucose control) could significantly reverse its adverse effect in an AMPK-mTOR pathway dependent manner. Metformin 29-38 mechanistic target of rapamycin kinase Homo sapiens 199-203 30988378-6 2019 Metformin specifically decreased IL-6R expression which is mediated via AMPK, mTOR, and miR34a. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 78-82 31348946-7 2019 However, there is a growing understanding that Metformin demonstrates its anti-epileptic effect mainly via ameliorating brain oxidative damage, activation of AMPK, inhibition of mTOR pathway, downregulation of alpha-synuclein, reducing apoptosis, downregulation of BDNF and TrkB level. Metformin 47-56 mechanistic target of rapamycin kinase Homo sapiens 178-182 31324361-4 2019 Metformin"s main antineoplastic mechanism of action is thought to be mediated through inhibition of mammalian target of rapamycin, inhibition of hypoxia-inducible factor 1 (HIF-1) alpha, and activation of p53. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 100-129 31135975-1 2019 The diabetes mellitus (DM) drug metformin targets mechanistic/mammalian target of rapamycin and inhibits lymphoma growth in vitro. Metformin 32-41 mechanistic target of rapamycin kinase Homo sapiens 62-91 31284427-0 2019 Metformin Enhances Nomegestrol Acetate Suppressing Growth of Endometrial Cancer Cells and May Correlate to Downregulating mTOR Activity In Vitro and In Vivo. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 122-126 31173255-8 2019 In addition, compared with the control group, metformin significantly enhanced the activity of caspase-3, increased the expression of AMPK/pAMPK/Bax proteins and reduced the expression of mTOR/Bcl-2 proteins (P<0.05). Metformin 46-55 mechanistic target of rapamycin kinase Homo sapiens 188-192 31173255-10 2019 Metformin may inhibit glioma cell proliferation, migration and invasion, and promote its apoptosis; the effects may be associated with the AMPK/mTOR signaling pathway and oxidative stress. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 144-148 30945296-10 2019 Moreover, gingival tissue exhibited less macrophage infiltration and decreased expression of Nek7, NLRP3, caspase-1, and mammalian target of rapamycin (mTOR), which were simultaneously observed in RAW 264.7 cell models stimulated with metformin. Metformin 235-244 mechanistic target of rapamycin kinase Homo sapiens 121-150 30989716-12 2019 We also discuss the activation of AMP activated protein kinase (AMPK) by the most widely used drug for type 2 diabetes, metformin, which exerts a dual negative regulatory effect on mTOR and BMP signaling, suggesting that metformin is a promising drug treatment for HO. Metformin 120-129 mechanistic target of rapamycin kinase Homo sapiens 181-185 30989716-12 2019 We also discuss the activation of AMP activated protein kinase (AMPK) by the most widely used drug for type 2 diabetes, metformin, which exerts a dual negative regulatory effect on mTOR and BMP signaling, suggesting that metformin is a promising drug treatment for HO. Metformin 221-230 mechanistic target of rapamycin kinase Homo sapiens 181-185 31284427-7 2019 Metformin significantly increased the inhibitory effect of and apoptosis induced by NOMAC and strengthened the depressive effect of NOMAC on activity of mTOR and its downstream substrates, compared to their treatment alone (p < 0.05). Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 153-157 30445633-9 2019 Treatment of metformin led to activation of AMP-activated protein kinase (AMPK) and attenuated signaling of the downstream molecules such as p-mTOR, p-p70S6K and cyclin D1 expression both in vivo and in vitro. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 143-147 31284427-8 2019 In xenograft tumor tissues, metformin (100 mg/kg) enhanced the suppressive effect of NOMAC (100 mg/kg) on mTOR signaling and increased the average concentration of NOMAC by nearly 1.6 times compared to NOMAC treatment alone. Metformin 28-37 mechanistic target of rapamycin kinase Homo sapiens 106-110 30445633-10 2019 Taken together, our study demonstrated that metformin suppressed the carcinogenesis of ESCC through inhibiting AMPK/mammalian target of the rapamycin (mTOR) signaling pathway, resulting in its chemopreventive effects on the carcinogenesis of ESCC. Metformin 44-53 mechanistic target of rapamycin kinase Homo sapiens 151-155 31028998-6 2019 More importantly, metformin induced G2/M cell cycle phase arrest in RA-FLS via the IGF-IR/PI3K/AKT/ m-TOR pathway and inhibited m-TOR phosphorylation through both the IGF-IR/PI3K/AKT signaling pathways thereby further upregulating and down-regulating p70s6k and 4E-BP1 phosphorylation, respectively; however, metformin was found not to induce apoptosis in RA-FLSs. Metformin 18-27 mechanistic target of rapamycin kinase Homo sapiens 100-105 31028998-6 2019 More importantly, metformin induced G2/M cell cycle phase arrest in RA-FLS via the IGF-IR/PI3K/AKT/ m-TOR pathway and inhibited m-TOR phosphorylation through both the IGF-IR/PI3K/AKT signaling pathways thereby further upregulating and down-regulating p70s6k and 4E-BP1 phosphorylation, respectively; however, metformin was found not to induce apoptosis in RA-FLSs. Metformin 18-27 mechanistic target of rapamycin kinase Homo sapiens 128-133 30753544-3 2019 RESULTS: Metformin added to peripheral blood mononuclear cells from healthy volunteers enhanced in vitro cellular metabolism while inhibiting the mammalian target of rapamycin targets p70S6K and 4EBP1, with decreased cytokine production and cellular proliferation and increased phagocytosis activity. Metformin 9-18 mechanistic target of rapamycin kinase Homo sapiens 146-175 30753544-4 2019 Metformin administered to healthy human volunteers led to significant downregulation of genes involved in oxidative phosphorylation, mammalian target of rapamycin signaling, and type I interferon response pathways, particularly following stimulation with M. tuberculosis, and upregulation of genes involved in phagocytosis and reactive oxygen species production was increased. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 133-162 31321352-3 2019 Metformin suppresses the mammalian target of rapamycin (mTOR) and our previous study showed that it also inhibits the activity of extracellular signal-regulated kinase (ERK). Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 25-54 31321352-3 2019 Metformin suppresses the mammalian target of rapamycin (mTOR) and our previous study showed that it also inhibits the activity of extracellular signal-regulated kinase (ERK). Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 56-60 31020710-9 2019 Expression of phosphorylated AMPK was increased and that of phosphorylated mammalian target of rapamycin (mTOR) was decreased after exposure to tHA plus metformin. Metformin 153-162 mechanistic target of rapamycin kinase Homo sapiens 75-104 31020710-9 2019 Expression of phosphorylated AMPK was increased and that of phosphorylated mammalian target of rapamycin (mTOR) was decreased after exposure to tHA plus metformin. Metformin 153-162 mechanistic target of rapamycin kinase Homo sapiens 106-110 30894020-4 2019 It found that in aged ApoE3-TR mice, metformin treatment, at a molecular level, inhibited AMPK activity, increased insulin signaling, and activated mammalian target of rapamycin signaling, resulting in an enhanced expression of postsynaptic proteins; but the response of the neuronal AMPK activity and insulin signaling to metformin was blunt in aged ApoE4-TR mice. Metformin 37-46 mechanistic target of rapamycin kinase Homo sapiens 148-177 31042624-4 2019 This study shows that metformin suppressed CD133 expression mainly by affecting the CD133 P1 promoter via adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling but not the mammalian target of rapamycin (mTOR). Metformin 22-31 mechanistic target of rapamycin kinase Homo sapiens 221-225 30334569-0 2019 Metformin inhibits mTOR-HIF-1alpha axis and profibrogenic and inflammatory biomarkers in thioacetamide-induced hepatic tissue alterations. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 19-23 30334569-2 2019 Therefore, we tested whether metformin can protect against liver injuries including fibrosis induced by TAA possibly via the downregulation of mTOR-HIF-1alpha axis and profibrogenic and inflammatory biomarkers. Metformin 29-38 mechanistic target of rapamycin kinase Homo sapiens 143-147 30816444-2 2019 Metformin is used as a first-line drug for the treatment of type 2 diabetes; however, drug repositioning studies have revealed its antitumor effects, mainly mediated through AMP-activated protein kinase (AMPK) activation and AKT/mammalian target of rapamycin (mTOR) pathway inhibition in various types of cancer, including drug-resistant cancer cells. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 229-258 30814053-0 2019 mTOR inhibition by metformin impacts monosodium urate crystal-induced inflammation and cell death in gout: a prelude to a new add-on therapy? Metformin 19-28 mechanistic target of rapamycin kinase Homo sapiens 0-4 30814053-10 2019 By inhibiting mTOR signalling with metformin or rapamycin, a reduction of cell death and release of inflammatory mediators was observed. Metformin 35-44 mechanistic target of rapamycin kinase Homo sapiens 14-18 30814053-11 2019 Consistent with this, we show that patients with gout who are treated with the mTOR inhibitor metformin have a lower frequency of gout attacks. Metformin 94-103 mechanistic target of rapamycin kinase Homo sapiens 79-83 30816444-2 2019 Metformin is used as a first-line drug for the treatment of type 2 diabetes; however, drug repositioning studies have revealed its antitumor effects, mainly mediated through AMP-activated protein kinase (AMPK) activation and AKT/mammalian target of rapamycin (mTOR) pathway inhibition in various types of cancer, including drug-resistant cancer cells. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 260-264 29848180-9 2019 In addition, metformin increased phosphorylation of AMPK in a dose-dependent manner (10-200 micromol/L) indicating an effect on mammalian target of rapamycin (mTOR) signaling. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 128-157 30670777-6 2019 Rapamycin, a lactate transport blocker and metformin were used as modulators of the Akt-mTOR pathway and cell metabolism. Metformin 43-52 mechanistic target of rapamycin kinase Homo sapiens 88-92 29848180-9 2019 In addition, metformin increased phosphorylation of AMPK in a dose-dependent manner (10-200 micromol/L) indicating an effect on mammalian target of rapamycin (mTOR) signaling. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 159-163 29848180-10 2019 Our data suggest that metformin therapy represents a potential fertility-sparing option for women with early-stage EC, given its capacity to inhibit EC cell proliferation, ERalpha expression, and the mTOR cell proliferation pathway. Metformin 22-31 mechanistic target of rapamycin kinase Homo sapiens 200-204 30720062-0 2019 Metformin triggers the intrinsic apoptotic response in human AGS gastric adenocarcinoma cells by activating AMPK and suppressing mTOR/AKT signaling. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 129-133 31005944-9 2019 Treatment of non-diabetic individuals with metformin controls inflammation by improving glucose metabolism and by regulating intracellular immunometabolic checkpoints such as the adenosin 5 monophosphate activated protein kinase and mammalian target of rapamycin, in association with microbiota modification. Metformin 43-52 mechanistic target of rapamycin kinase Homo sapiens 233-262 31114366-3 2019 Metformin inhibits mTOR activity by activating ATM (ataxia telangiectasia mutated) and LKB1 (liver kinase B1) and then adenosine monophosphate-activated kinase (AMPK), and thus prevents protein synthesis and cell growth. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 19-23 31205529-9 2019 Metformin inhibited mammalian target of rapamycin (mTOR) by activation of tuberous sclerosis complex 2 (TSC-2) through phosphorylation of adenosine monophosphate-activated protein kinase at threonine-172 (AMPKThr172). Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 20-49 31205529-9 2019 Metformin inhibited mammalian target of rapamycin (mTOR) by activation of tuberous sclerosis complex 2 (TSC-2) through phosphorylation of adenosine monophosphate-activated protein kinase at threonine-172 (AMPKThr172). Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 51-55 31249600-8 2019 We correlate the metformin-induced delay in satellite cell activation with the inhibition of the ribosome protein RPS6, one of the downstream effectors of the mTOR pathway. Metformin 17-26 mechanistic target of rapamycin kinase Homo sapiens 159-163 30552782-7 2019 Suppression of LKB1 or promotion of AMP by metformin also abrogated the hyperproliferative phenotype caused by SIRT4 loss, which further confirmed that the LKB1/AMPKalpha/mTOR axis is required in SIRT4-deficiency-promoted HCC tumorigenesis. Metformin 43-52 mechanistic target of rapamycin kinase Homo sapiens 171-175 30720062-5 2019 Western blot analysis demonstrated that treatment with metformin increased the phosphorylation of AMPK, and decreased the phosphorylation of AKT, mTOR and p70S6k. Metformin 55-64 mechanistic target of rapamycin kinase Homo sapiens 146-150 30905926-0 2019 Neuro-Protective Role of Metformin in Patients with Acute Stroke and Type 2 Diabetes Mellitus via AMPK/Mammalian Target of Rapamycin (mTOR) Signaling Pathway and Oxidative Stress. Metformin 25-34 mechanistic target of rapamycin kinase Homo sapiens 103-132 30917505-8 2019 Interestingly, p-mTOR was higher in patients with metabolic syndrome than those with different etiology, and, similar to SIRT-3, in metformin-treated than insulin-treated patients. Metformin 132-141 mechanistic target of rapamycin kinase Homo sapiens 17-21 30575815-6 2019 In vitro, glucose, insulin, VEGFA and hypoxia upregulated endothelial FABP4, which was reversed by metformin through mTOR pathway inhibition. Metformin 99-108 mechanistic target of rapamycin kinase Homo sapiens 117-121 30849634-5 2019 As expected, metformin increased the phosphorylation of AMPK and decreased the panobinostat-caused phosphorylation of S6 ribosomal protein, thus inhibiting the panobinostat-activated mTOR pathway. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 183-187 30905926-0 2019 Neuro-Protective Role of Metformin in Patients with Acute Stroke and Type 2 Diabetes Mellitus via AMPK/Mammalian Target of Rapamycin (mTOR) Signaling Pathway and Oxidative Stress. Metformin 25-34 mechanistic target of rapamycin kinase Homo sapiens 134-138 30905926-11 2019 CONCLUSIONS Metformin can improve the neurological function and oxidative stress status of acute stroke patients with type 2 diabetes, and its mechanism may be related to the AMPK/mTOR signaling pathway and oxidative stress. Metformin 12-21 mechanistic target of rapamycin kinase Homo sapiens 180-184 30899369-0 2019 Metformin induces the M2 macrophage polarization to accelerate the wound healing via regulating AMPK/mTOR/NLRP3 inflammasome singling pathway. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 101-105 30146703-0 2019 In vitro evaluation of effects of metformin on morphine and methadone tolerance through mammalian target of rapamycin signaling pathway. Metformin 34-43 mechanistic target of rapamycin kinase Homo sapiens 88-117 30146703-3 2019 Metformin activates 5" adenosine monophosphate-activated protein kinase (AMPK) which directly suppresses the mTOR complex 1 signaling pathway. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 109-113 30146703-4 2019 On the other hand, metformin can also inhibit mTOR directly and in an AMPK-independent manner. Metformin 19-28 mechanistic target of rapamycin kinase Homo sapiens 46-50 30779140-11 2019 Moreover, gingival tissue exhibited less macrophage infiltration and decreased expression of Nek7, NLRP3, caspase-1 and mammalian target of rapamycin (mTOR), which were simultaneously observed in RAW 264.7 cell models stimulated with metformin. Metformin 234-243 mechanistic target of rapamycin kinase Homo sapiens 120-149 30146703-9 2019 Contribution of mTOR signaling pathway in metformin-induced effect was shown by the inhibition of phosphorylation of S6K1 and 4E-BP1, the downstream targets of mTOR. Metformin 42-51 mechanistic target of rapamycin kinase Homo sapiens 16-20 30146703-9 2019 Contribution of mTOR signaling pathway in metformin-induced effect was shown by the inhibition of phosphorylation of S6K1 and 4E-BP1, the downstream targets of mTOR. Metformin 42-51 mechanistic target of rapamycin kinase Homo sapiens 160-164 30899369-10 2019 Furthermore, blockage of AMPK or activation of mTOR abolished the effects of metformin treatment on depressing NLRP3 inflammasome activation, M2 polarization and improving wound healing. Metformin 77-86 mechanistic target of rapamycin kinase Homo sapiens 47-51 30899369-11 2019 It suggested that the treatment effects of metformin on wound healing were through regulating AMPK/mTOR/NLRP3 inflammasome signaling axis. Metformin 43-52 mechanistic target of rapamycin kinase Homo sapiens 99-103 30899369-12 2019 CONCLUSION: Metformin regulated AMPK/mTOR singling pathway to inhibit NLRP3 inflammasome activation, which boosted M2 macrophage polarization to accelerate the wound healing. Metformin 12-21 mechanistic target of rapamycin kinase Homo sapiens 37-41 30755615-4 2019 Second, we found that molecular activation of small intestinal mTOR blunts the glucose-lowering effect of the oral anti-diabetic agent metformin, while inhibiting small intestinal mTOR alone lowers plasma glucose levels by inhibiting glucose production in rodents with diabetes as well. Metformin 135-144 mechanistic target of rapamycin kinase Homo sapiens 63-67 30626087-10 2019 Furthermore, metformin (2 mM) inhibited the mTOR pathway and its downstream components under zero glucose/glucose-starved conditions indicating that using metformin in combination with agents that inhibit the glycolytic pathway should be more beneficial for the treatment of triple-negative breast cancers in diabetic individuals. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 44-48 30626087-10 2019 Furthermore, metformin (2 mM) inhibited the mTOR pathway and its downstream components under zero glucose/glucose-starved conditions indicating that using metformin in combination with agents that inhibit the glycolytic pathway should be more beneficial for the treatment of triple-negative breast cancers in diabetic individuals. Metformin 155-164 mechanistic target of rapamycin kinase Homo sapiens 44-48 30290005-7 2019 Because of its effect on the mTOR pathway, there may be a role for metformin in slowing or reversing growth of life-threatening hamartomas in tuberous sclerosis complex. Metformin 67-76 mechanistic target of rapamycin kinase Homo sapiens 29-33 32160445-2 2019 mTOR protein kinase is an perspective therapeutic target for the treatment of multiple cancers, both with the mTOR inhibitors themselves (rapamycin and its derivatives) and in combination with inhibitors of other pathways (for example, metformin). Metformin 236-245 mechanistic target of rapamycin kinase Homo sapiens 0-4 30290005-0 2019 The journey of metformin from glycaemic control to mTOR inhibition and the suppression of tumour growth. Metformin 15-24 mechanistic target of rapamycin kinase Homo sapiens 51-55 30025915-14 2018 Furthermore, metformin promoted AMP-activated protein kinase (AMPK) phosphorylation but inhibited insulin-like growth factor-1 receptor (IGF-1R) expression, protein kinase B (PKB/AKT) phosphorylation and mammalian target of rapamycin (mTOR) phosphorylation. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 204-233 30019648-9 2019 Metformin is AMPK activators that can suppress mTOR, STAT3 and HIF-1 so AMPK activation plays important role in suppressing inflammation and osteoclastogenesis and decreasing cancer. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 47-51 30019648-10 2019 CONCLUSION: Metformin effect on AMPK and mTOR pathways gives the capability to change Treg/Th17 balance and decrease Th17 differentiation and inflammation, osteoclastogenesis and cancers in RA patients. Metformin 12-21 mechanistic target of rapamycin kinase Homo sapiens 41-45 30888659-6 2019 Resveratrol, rapamycin, metformin and aspirin, showing effectiveness in model organism life- and healthspan extension mainly target the master regulators of aging such as mTOR, FOXO and PGC1alpha, affecting autophagy, inflammation and oxidative stress. Metformin 24-33 mechanistic target of rapamycin kinase Homo sapiens 171-175 30745824-0 2019 Metformin Promotes the Survival of Random-Pattern Skin Flaps by Inducing Autophagy via the AMPK-mTOR-TFEB signaling pathway. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 96-100 30745824-6 2019 Moreover, metformin also activated the AMPK-mTOR-TFEB signaling pathway in ischemic areas. Metformin 10-19 mechanistic target of rapamycin kinase Homo sapiens 44-48 30745824-7 2019 Inhibitions of AMPK via Compound C (CC) or AMPK shRNA adeno-associated virus (AAV) vector resulted in the downregulation of the AMPK-mTOR-TFEB signaling pathway and autophagy level in metformin-treated flaps. Metformin 184-193 mechanistic target of rapamycin kinase Homo sapiens 133-137 30025915-14 2018 Furthermore, metformin promoted AMP-activated protein kinase (AMPK) phosphorylation but inhibited insulin-like growth factor-1 receptor (IGF-1R) expression, protein kinase B (PKB/AKT) phosphorylation and mammalian target of rapamycin (mTOR) phosphorylation. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 235-239 30132243-0 2018 Metformin Plus Caloric Restriction Show Anti-epileptic Effects Mediated by mTOR Pathway Inhibition. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 75-79 30308035-2 2018 Although inhibition of the mTOR pathway is known to be the most important mechanism for the antitumor effects of metformin, other mechanisms remain unclear. Metformin 113-122 mechanistic target of rapamycin kinase Homo sapiens 27-31 30259865-3 2018 In breast cancer cell lines, metformin has been shown to induce phosphorylation at specific serine sites in insulin regulated substrate of mTOR pathway that results in apoptosis over cell proliferation. Metformin 29-38 mechanistic target of rapamycin kinase Homo sapiens 139-143 30259865-4 2018 The author models and performs bifurcation analysis to simulate cell proliferation and apoptosis in mTOR signalling pathway to capture the dynamics both in the presence and absence of metformin in cancer cells. Metformin 184-193 mechanistic target of rapamycin kinase Homo sapiens 100-104 29807101-4 2018 A potential anti-tumourigenic effect of metformin may be mediated by its role in activating AMP-kinase, which in turn inhibits mammalian target of rapamycin (mTOR). Metformin 40-49 mechanistic target of rapamycin kinase Homo sapiens 127-156 29807101-4 2018 A potential anti-tumourigenic effect of metformin may be mediated by its role in activating AMP-kinase, which in turn inhibits mammalian target of rapamycin (mTOR). Metformin 40-49 mechanistic target of rapamycin kinase Homo sapiens 158-162 29434877-1 2018 Previous studies have suggested that metformin may improve the survival rate of patients with pancreatic cancer (PC) by regulating the adenosine monophosphate-activated protein kinase/mammalian target of rapamycin (mTOR) signaling pathway. Metformin 37-46 mechanistic target of rapamycin kinase Homo sapiens 184-213 30171812-0 2018 Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway. Metformin 23-32 mechanistic target of rapamycin kinase Homo sapiens 137-166 30171812-0 2018 Anticancer Activity of Metformin, an Antidiabetic Drug, Against Ovarian Cancer Cells Involves Inhibition of Cysteine-Rich 61 (Cyr61)/Akt/Mammalian Target of Rapamycin (mTOR) Signaling Pathway. Metformin 23-32 mechanistic target of rapamycin kinase Homo sapiens 168-172 29847773-0 2018 Metformin enhances cisplatin induced inhibition of cholangiocarcinoma cells via AMPK-mTOR pathway. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 85-89 29705631-5 2018 Metformin inhibited tumor cell proliferation and induced apoptosis through activation of AMPK/mTOR pathway and further influencing energy metabolism, phospholipid metabolism and glucose catabolism. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 94-98 29039022-9 2018 Interestingly, persistent enhancement of the mammalian target of rapamycin, dopamine D1 receptor, and extracellular signaling-regulated kinase 1/2 signaling was maintained in the DA-denervated striatum during metformin treatment. Metformin 209-218 mechanistic target of rapamycin kinase Homo sapiens 45-74 30023463-4 2018 We previously reported that metformin inhibits the phosphorylation of ERK and BEZ235, a dual inhibitor of PI3K and mTOR, has anti-tumor activity against HCT15 CRC cells harboring mutations of KRAS and PIK3CA. Metformin 28-37 mechanistic target of rapamycin kinase Homo sapiens 115-119 30023463-7 2018 Our study shows that both of the two signaling pathways can be blocked by this combinational strategy: metformin suppressed both pathways by inhibiting the phosphorylation of ERK, 4E-BP1 and S6, and BEZ235 suppressed PI3K/AKT/ mTOR pathway by reducing the phosphorylation of 4E-BP1 and S6. Metformin 103-112 mechanistic target of rapamycin kinase Homo sapiens 227-231 29182407-0 2018 Metformin is associated with reduced cell proliferation in human endometrial cancer by inbibiting PI3K/AKT/mTOR signaling. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 107-111 29182407-8 2018 Metformin significantly decreased proliferation in human endometrial cancer may by inhibiting PI3K/AKT/mTOR signaling. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 103-107 29662316-9 2018 Furthermore, our study revealed that metformin activated AMPK and suppressed mTOR and HIF1alpha expression. Metformin 37-46 mechanistic target of rapamycin kinase Homo sapiens 77-81 29662316-12 2018 Conclusion: Taken together, these results indicated that metformin may play an important role in modulating CD19-CAR T cell biological functions in an AMPK-dependent and mTOR/HIF1alpha-independent manner. Metformin 57-66 mechanistic target of rapamycin kinase Homo sapiens 170-174 29285837-0 2018 New metformin derivative HL156A prevents oral cancer progression by inhibiting the insulin-like growth factor/AKT/mammalian target of rapamycin pathways. Metformin 4-13 mechanistic target of rapamycin kinase Homo sapiens 114-143 30111296-11 2018 This cytotoxic effect was profound upon incorporation of metformin, an indirect mTOR inhibitor, in cisplatin nano-cubosomes. Metformin 57-66 mechanistic target of rapamycin kinase Homo sapiens 80-84 29948021-2 2018 Metformin may potentiate mTOR inhibition by sirolimus while mitigating its adverse effects. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 25-29 29922884-0 2018 Comment on "Targeting AMPK, mTOR and beta-Catenin by Combined Metformin and Aspirin Therapy in HCC: An Appraisal in Egyptian HCC Patients". Metformin 62-71 mechanistic target of rapamycin kinase Homo sapiens 28-32 29871814-7 2018 Therefore, the immunocorrective potentials of modified IL-2 and the anti-diabetic drug metformin are thoroughly discussed in the context of tumor immunobiology, mTOR pathways and revised Warburg effect. Metformin 87-96 mechanistic target of rapamycin kinase Homo sapiens 161-165 29482945-8 2018 Furthermore, metformin could increase anti-proliferative effects of mTORC1 and PI3K/mTOR inhibitors as well as natural products such as berberine and the anti-malarial drug chloroquine in certain PDAC lines. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 68-72 29728793-0 2018 Metformin Protects Against Spinal Cord Injury by Regulating Autophagy via the mTOR Signaling Pathway. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 78-82 29728793-8 2018 Western blot and immunofluorescent analysis revealed that mammalian target of rapamycin (mTOR) and P70S6 kinase (P70S6K) decreased, while the expression of autophagy markers increased and apoptosis markers declined in animals treated with metformin following SCI. Metformin 239-248 mechanistic target of rapamycin kinase Homo sapiens 58-87 29728793-9 2018 Taken together, these findings suggest that metformin functions as a neuroprotective agent following SCI by promoting autophagy and inhibiting apoptosis by regulating the mTOR/P70S6K signaling pathway. Metformin 44-53 mechanistic target of rapamycin kinase Homo sapiens 171-175 29576625-8 2018 Metformin and phenformin decreased mTOR activity in chondrosarcoma cells, and metformin decreased LC3B-II levels, which is counteracted by chloroquine. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 35-39 29467552-11 2018 The inhibitory effects of metformin on activated HSCs were mediated by inhibiting the Akt/mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) pathways via the activation of adenosine monophosphate-activated protein kinase (AMPK). Metformin 26-35 mechanistic target of rapamycin kinase Homo sapiens 90-119 29467552-11 2018 The inhibitory effects of metformin on activated HSCs were mediated by inhibiting the Akt/mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) pathways via the activation of adenosine monophosphate-activated protein kinase (AMPK). Metformin 26-35 mechanistic target of rapamycin kinase Homo sapiens 121-125 29342230-2 2018 To uncover the anti-cancer mechanisms of metformin, preclinical studies determined that metformin impairs cellular metabolism and suppresses oncogenic signaling pathways, including receptor tyrosine kinase, PI3K/Akt, and mTOR pathways. Metformin 41-50 mechanistic target of rapamycin kinase Homo sapiens 221-225 29342230-2 2018 To uncover the anti-cancer mechanisms of metformin, preclinical studies determined that metformin impairs cellular metabolism and suppresses oncogenic signaling pathways, including receptor tyrosine kinase, PI3K/Akt, and mTOR pathways. Metformin 88-97 mechanistic target of rapamycin kinase Homo sapiens 221-225 29094287-3 2018 OBJECTIVE: The current work aimed to investigate the possibility of targeting AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and beta-catenin proteins through combined metformin/aspirin treatment in the HepG2 cell line, and to explore such molecular targets in Egyptian HCC patients. Metformin 196-205 mechanistic target of rapamycin kinase Homo sapiens 115-144 29094287-3 2018 OBJECTIVE: The current work aimed to investigate the possibility of targeting AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and beta-catenin proteins through combined metformin/aspirin treatment in the HepG2 cell line, and to explore such molecular targets in Egyptian HCC patients. Metformin 196-205 mechanistic target of rapamycin kinase Homo sapiens 146-150 29094287-7 2018 RESULTS: Metformin/aspirin combined treatment had a synergistic effect on cell cycle arrest at the G2/M phase and apoptosis induction in a caspase-dependent manner via downregulation of pAMPK and mTOR protein expression. Metformin 9-18 mechanistic target of rapamycin kinase Homo sapiens 196-200 29094287-10 2018 CONCLUSIONS: Targeting AMPK, mTOR and beta-catenin by combined metformin/aspirin treatment could be a promising therapeutic strategy for Egyptian HCC patients, and possibly other HCC patients. Metformin 63-72 mechanistic target of rapamycin kinase Homo sapiens 29-33 29434877-1 2018 Previous studies have suggested that metformin may improve the survival rate of patients with pancreatic cancer (PC) by regulating the adenosine monophosphate-activated protein kinase/mammalian target of rapamycin (mTOR) signaling pathway. Metformin 37-46 mechanistic target of rapamycin kinase Homo sapiens 215-219 29434877-6 2018 Additionally, metformin (20 mmol/l) + rapamycin (200 ng/ml) significantly suppressed the expression of phosphorylated mTOR compared with metformin or rapamycin alone. Metformin 14-23 mechanistic target of rapamycin kinase Homo sapiens 118-122 29434877-6 2018 Additionally, metformin (20 mmol/l) + rapamycin (200 ng/ml) significantly suppressed the expression of phosphorylated mTOR compared with metformin or rapamycin alone. Metformin 137-146 mechanistic target of rapamycin kinase Homo sapiens 118-122 29385181-0 2018 Simvastatin and metformin inhibit cell growth in hepatitis C virus infected cells via mTOR increasing PTEN and autophagy. Metformin 16-25 mechanistic target of rapamycin kinase Homo sapiens 86-90 29385181-7 2018 Simvastatin and metformin co-administered down-regulated mTOR and TCTP, while PTEN was increased. Metformin 16-25 mechanistic target of rapamycin kinase Homo sapiens 57-61 29385181-10 2018 In human primary hepatocytes, metformin treatment inhibited mTOR and PTEN, but up-regulated p62, LC3BII and Caspase 3. Metformin 30-39 mechanistic target of rapamycin kinase Homo sapiens 60-64 29323154-10 2018 In conclusion, the effect of metformin on CSCs varies depending on the AMPK-mTOR and glutamine metabolism. Metformin 29-38 mechanistic target of rapamycin kinase Homo sapiens 76-80 30067448-9 2018 However, tissue TMA analyses by IHC showed decreased mTOR activation, as indicated by phospho-mTOR in cancer tissue of patients with metformin and also with insulin use compared to the control group. Metformin 133-142 mechanistic target of rapamycin kinase Homo sapiens 53-57 29779024-1 2018 BACKGROUND: Metformin inhibits cyclic AMP generation and activates AMP-activated protein kinase (AMPK), which inhibits the cystic fibrosis transmembrane conductance regulator and Mammalian Target of Rapamycin pathways. Metformin 12-21 mechanistic target of rapamycin kinase Homo sapiens 179-208 30067448-9 2018 However, tissue TMA analyses by IHC showed decreased mTOR activation, as indicated by phospho-mTOR in cancer tissue of patients with metformin and also with insulin use compared to the control group. Metformin 133-142 mechanistic target of rapamycin kinase Homo sapiens 94-98 30032136-14 2018 The metformin/FTY720 regimen markedly induced ROS generation; moreover, apoptosis, ER stress and inhibition of PI3K/AKT/ mTOR were attenuated by the ROS scavenger NAC. Metformin 4-13 mechanistic target of rapamycin kinase Homo sapiens 121-125 33385166-6 2018 In addition, metformin reduces cellular proliferation by decreasing the amount of available insulin or by directly affecting the mammalian target of rapamycin complex involved with regulating protein synthesis. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 129-158 29165314-2 2017 Metformin and rapamycin are two FDA-approved mTOR inhibitors proposed for this purpose, exhibiting significant anti-cancer and anti-aging properties beyond their current clinical applications. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 45-49 29422962-5 2018 Studies have demonstrated that reducing insulin and insulin-like growth factor levels in the peripheral blood circulation may lead to the inhibition of phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin (mTOR) signaling or activation of AMP-activated protein kinase, which inhibits mTOR signaling, a process that may be associated with the antitumor effect of metformin. Metformin 371-380 mechanistic target of rapamycin kinase Homo sapiens 215-219 29467947-0 2018 Metformin inhibits TGF-beta1-induced epithelial-to-mesenchymal transition-like process and stem-like properties in GBM via AKT/mTOR/ZEB1 pathway. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 127-131 29467947-8 2018 We further clarified that metformin specifically inhibited TGF-beta1 activated AKT, the downstream molecular mTOR and the leading transcription factor ZEB1. Metformin 26-35 mechanistic target of rapamycin kinase Homo sapiens 109-113 29467947-9 2018 Taken together, our data demonstrate that metformin inhibits TGF-beta1-induced EMT-like process and cancer stem-like properties in GBM cells via AKT/mTOR/ZEB1 pathway and provide evidence of metformin for further clinical investigation targeted GBM. Metformin 42-51 mechanistic target of rapamycin kinase Homo sapiens 149-153 28964970-3 2017 The cytotoxic effect of metformin correlated with intracellular reactive oxygen species reduction, activation of AMPK, the inhibition of pro-survival pathways such as mTOR and STAT3 and the down-regulation of v-FLIP, a latent viral antigen that also plays a pivotal role in PEL cell survival. Metformin 24-33 mechanistic target of rapamycin kinase Homo sapiens 167-171 29167573-6 2017 The anti-proliferative action of metformin was mediated by two different mechanisms: AMPK activation and increase in the production of reactive oxygen species, which suppressed the mTOR pathway and its downstream targets S6 and 4EBP1. Metformin 33-42 mechanistic target of rapamycin kinase Homo sapiens 181-185 28319830-1 2017 Metformin is an oral hypoglycemic drug that has been shown to inhibit cancer cell proliferation via up-regulation of AMPK (AMP-activated protein kinase), and possibly inhibition of mTOR (mammalian target of rapamycin). Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 181-185 29085506-6 2017 Metformin significantly decreased E2-stimulated cell proliferation; an effect that was rescued in the presence of compound C. Metformin treatment markedly increased the phosphorylation of AMPK while decreasing p70S6K phosphorylation, indicating that metformin exerts its effects through stimulation of AMPK and subsequent inhibition of the mammalian target of rapamycin (mTOR) signaling pathway. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 340-369 29085506-6 2017 Metformin significantly decreased E2-stimulated cell proliferation; an effect that was rescued in the presence of compound C. Metformin treatment markedly increased the phosphorylation of AMPK while decreasing p70S6K phosphorylation, indicating that metformin exerts its effects through stimulation of AMPK and subsequent inhibition of the mammalian target of rapamycin (mTOR) signaling pathway. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 371-375 29085506-6 2017 Metformin significantly decreased E2-stimulated cell proliferation; an effect that was rescued in the presence of compound C. Metformin treatment markedly increased the phosphorylation of AMPK while decreasing p70S6K phosphorylation, indicating that metformin exerts its effects through stimulation of AMPK and subsequent inhibition of the mammalian target of rapamycin (mTOR) signaling pathway. Metformin 126-135 mechanistic target of rapamycin kinase Homo sapiens 340-369 29085506-6 2017 Metformin significantly decreased E2-stimulated cell proliferation; an effect that was rescued in the presence of compound C. Metformin treatment markedly increased the phosphorylation of AMPK while decreasing p70S6K phosphorylation, indicating that metformin exerts its effects through stimulation of AMPK and subsequent inhibition of the mammalian target of rapamycin (mTOR) signaling pathway. Metformin 126-135 mechanistic target of rapamycin kinase Homo sapiens 371-375 29085506-8 2017 Reverse transcription-quantitative polymerase chain reaction analysis demonstrated that c-fos and c-myc expression were attenuated by metformin, an effect that was rescued in the presence of compound C. Therefore, metformin regulates the expression of ERs, and inhibits estrogen-mediated proliferation of human EC cells through the activation of AMPK and subsequent inhibition of the mTOR signaling pathway. Metformin 134-143 mechanistic target of rapamycin kinase Homo sapiens 384-388 29085506-8 2017 Reverse transcription-quantitative polymerase chain reaction analysis demonstrated that c-fos and c-myc expression were attenuated by metformin, an effect that was rescued in the presence of compound C. Therefore, metformin regulates the expression of ERs, and inhibits estrogen-mediated proliferation of human EC cells through the activation of AMPK and subsequent inhibition of the mTOR signaling pathway. Metformin 214-223 mechanistic target of rapamycin kinase Homo sapiens 384-388 28319830-6 2017 To evaluate the role of mTOR inhibition in metformin-induced cell death, Western blot was performed. Metformin 43-52 mechanistic target of rapamycin kinase Homo sapiens 24-28 28319830-1 2017 Metformin is an oral hypoglycemic drug that has been shown to inhibit cancer cell proliferation via up-regulation of AMPK (AMP-activated protein kinase), and possibly inhibition of mTOR (mammalian target of rapamycin). Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 187-216 29137418-2 2017 Metformin has been shown to inhibit mTOR pathway, with more favorable safety profile, leading to this hypothesis-generating trial to assess whether metformin enhances the efficacy of aromatase inhibitors. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 36-40 29340030-3 2017 Metformin potently inhibited growth in a dose-dependent manner in all four human OC cell lines through AMPK/mTOR pathways. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 108-112 27857021-9 2017 Further study revealed that metformin could suppress the expression of insulin-like growth factor 1 receptor and its downstream proteins, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT/PKB), phosphorylation of AKT (pAKT), mammalian target of rapamycin (mTOR), p70S6K, and PKM2. Metformin 28-37 mechanistic target of rapamycin kinase Homo sapiens 231-260 28732480-5 2017 In addition, metformin is a potent activator of activated protein kinase (AMPK) which in turn inhibits the mammalian target of rapamycin (mTOR) and other signal transduction mechanisms. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 107-136 28732480-5 2017 In addition, metformin is a potent activator of activated protein kinase (AMPK) which in turn inhibits the mammalian target of rapamycin (mTOR) and other signal transduction mechanisms. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 138-142 28525374-0 2017 The effect of rapamycin, NVP-BEZ235, aspirin, and metformin on PI3K/AKT/mTOR signaling pathway of PIK3CA-related overgrowth spectrum (PROS). Metformin 50-59 mechanistic target of rapamycin kinase Homo sapiens 72-76 28525374-6 2017 We assessed the therapeutic effects of four compounds (rapamycin, NVP-BEZ235, aspirin, and metformin) on PI3K/AKT/mTOR signaling pathway and cell growth. Metformin 91-100 mechanistic target of rapamycin kinase Homo sapiens 114-118 27857021-14 2017 CONCLUSION: Metformin restrained esophageal cancer cell proliferation partly by suppressing the PI3K/AKT/mTOR pathway. Metformin 12-21 mechanistic target of rapamycin kinase Homo sapiens 105-109 27857021-9 2017 Further study revealed that metformin could suppress the expression of insulin-like growth factor 1 receptor and its downstream proteins, phosphoinositide 3-kinase (PI3K), protein kinase B (AKT/PKB), phosphorylation of AKT (pAKT), mammalian target of rapamycin (mTOR), p70S6K, and PKM2. Metformin 28-37 mechanistic target of rapamycin kinase Homo sapiens 262-266 28168653-12 2017 High-dose metformin significantly reduced the expression of matrix metalloproteinase-2 (MMP-2) and mechanistic Target of Rapamycin (mTor), regardless of the concentration of dexamethasone and testosterone. Metformin 10-19 mechanistic target of rapamycin kinase Homo sapiens 99-130 28464864-0 2017 Metformin produces growth inhibitory effects in combination with nutlin-3a on malignant mesothelioma through a cross-talk between mTOR and p53 pathways. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 130-134 28464864-10 2017 Western blot analyses showed that metformin inhibited downstream pathways of the mammalian target of rapamycin (mTOR) but did not activate the p53 pathways, whereas nutlin-3a phosphorylated p53 and suppressed mTOR pathways. Metformin 34-43 mechanistic target of rapamycin kinase Homo sapiens 81-110 28464864-10 2017 Western blot analyses showed that metformin inhibited downstream pathways of the mammalian target of rapamycin (mTOR) but did not activate the p53 pathways, whereas nutlin-3a phosphorylated p53 and suppressed mTOR pathways. Metformin 34-43 mechanistic target of rapamycin kinase Homo sapiens 112-116 28339020-0 2017 Metformin inhibits endothelial progenitor cell migration by decreasing matrix metalloproteinases, MMP-2 and MMP-9, via the AMPK/mTOR/autophagy pathway. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 128-132 28168653-12 2017 High-dose metformin significantly reduced the expression of matrix metalloproteinase-2 (MMP-2) and mechanistic Target of Rapamycin (mTor), regardless of the concentration of dexamethasone and testosterone. Metformin 10-19 mechanistic target of rapamycin kinase Homo sapiens 132-136 28122334-2 2017 The drop in energy charge resulting from the metformin mediated inhibition of mitochondrial activity affects the function of the nuclear pore complex, blocks mTOR signaling and enhances the expression of ACAD10. Metformin 45-54 mechanistic target of rapamycin kinase Homo sapiens 158-162 28356082-9 2017 Everolimus combined with metformin additively inhibited cell survival, clonogenicity, mTOR signaling activity and mitochondrial respiration. Metformin 25-34 mechanistic target of rapamycin kinase Homo sapiens 86-90 28356082-12 2017 CONCLUSION: Metformin-induced effects are additive to the anti-proliferative and colony inhibitory properties of everolimus through inhibition of mitochondrial respiration and mTOR signaling. Metformin 12-21 mechanistic target of rapamycin kinase Homo sapiens 176-180 28196954-4 2017 Multiple studies in vitro and in vivo have demonstrated that metformin can inhibit the growth of thyroid cells and different types of thyroid cancer cells by affecting the insulin/IGF1 and mTOR pathways. Metformin 61-70 mechanistic target of rapamycin kinase Homo sapiens 189-193 28338172-11 2017 The results showed that metformin significantly inhibited the expression levels of key proteins of PI3K/Akt/mTOR signaling pathway. Metformin 24-33 mechanistic target of rapamycin kinase Homo sapiens 108-112 28052008-7 2017 Combination of metformin and 2-deoxyglucose initiated a strong metabolic stress in MCF-7/Dox cells via inhibiting glucose uptake, lactate, fatty acid, ATP production and protein kinase B(AKT)/ mammalian target of rapamycin(mTOR) pathway. Metformin 15-24 mechanistic target of rapamycin kinase Homo sapiens 193-228 27856287-4 2017 Spinal local application of AMPK agonist metformin (25mug) prevented the long term potentiation (LTP) induction and the activation of mTOR/p70S6K signal pathway, and significantly attenuated the acute thermal hyperalgesia and mechanical allodynia following single oxaliplatin treatment. Metformin 41-50 mechanistic target of rapamycin kinase Homo sapiens 134-138 27856287-8 2017 Local application of metformin significantly decreased the mTOR and p70S6K activation induced by tetanus stimulation or oxaliplatin (i.p.). Metformin 21-30 mechanistic target of rapamycin kinase Homo sapiens 59-63 27814614-3 2017 Here, we show that metformin induces growth inhibition and apoptosis through activating AMPK-mTOR pathway in human colorectal cancer cells. Metformin 19-28 mechanistic target of rapamycin kinase Homo sapiens 93-97 27803295-9 2017 Metformin significantly decreased subcutaneous tumour growth via cell-cycle block and mammalian target of rapamycin (mTOR) pathway inhibition, and also induced hypoxia and decreased angiogenesis. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 86-115 27803295-9 2017 Metformin significantly decreased subcutaneous tumour growth via cell-cycle block and mammalian target of rapamycin (mTOR) pathway inhibition, and also induced hypoxia and decreased angiogenesis. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 117-121 27919208-7 2017 Metformin inhibits cancer growth in colon by suppressing the colonic epithelial proliferation by inhibiting the mTOR pathway. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 112-116 27814614-5 2017 Moreover, ADORA1-mediated growth inhibition and apoptosis induced by metformin is AMPK-mTOR pathway dependent in human colorectal cancer cells. Metformin 69-78 mechanistic target of rapamycin kinase Homo sapiens 87-91 27959383-0 2017 Combination of metformin and sorafenib suppresses proliferation and induces autophagy of hepatocellular carcinoma via targeting the mTOR pathway. Metformin 15-24 mechanistic target of rapamycin kinase Homo sapiens 132-136 27576133-2 2016 It is widely accepted that metformin inhibits the growth of malignant cells primarily by suppressing the mTOR pathway or regulating autophagy. Metformin 27-36 mechanistic target of rapamycin kinase Homo sapiens 105-109 27920093-7 2017 MicroPET/CT imaging was performed to detect 18F-FDG uptake in vivo After treatment with metformin at 0, 2.5, 5 and 10 mM for 48 h, the ratio of p-AMPK to total AMPK showed significant rising in a dose-dependent manner in both BCPAP and KTC1, whereas p-AKT and p-mTOR expression level were downregulated. Metformin 88-97 mechanistic target of rapamycin kinase Homo sapiens 262-266 27745917-2 2016 In preclinical studies, metformin decreases endometrial cancer (EC) cell growth by activation of AMPK/mTOR inhibition. Metformin 24-33 mechanistic target of rapamycin kinase Homo sapiens 102-106 26733332-9 2016 High-glucose reduced AMPK phosphorylation and induced mammalian target of rapamycin (mTOR) activation in podocytes, which was abolished and reversed by pre-treatment with metformin. Metformin 171-180 mechanistic target of rapamycin kinase Homo sapiens 54-83 26733332-9 2016 High-glucose reduced AMPK phosphorylation and induced mammalian target of rapamycin (mTOR) activation in podocytes, which was abolished and reversed by pre-treatment with metformin. Metformin 171-180 mechanistic target of rapamycin kinase Homo sapiens 85-89 26733332-11 2016 In summary, metformin exhibits an anti-apoptotic impact on podocytes under high-glucose conditions via activation of AMPK and inhibition of mTOR signaling. Metformin 12-21 mechanistic target of rapamycin kinase Homo sapiens 140-144 27916907-10 2016 CONCLUSION: Metformin abolishes TGF-beta1-induced EMT in cervical carcinoma cells by inhibiting mTOR/p70s6k signaling to down-regulate PKM2 expression. Metformin 12-21 mechanistic target of rapamycin kinase Homo sapiens 96-100 27916907-0 2016 Metformin Inhibits TGF-beta1-Induced Epithelial-to-Mesenchymal Transition via PKM2 Relative-mTOR/p70s6k Signaling Pathway in Cervical Carcinoma Cells. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 92-96 27916907-8 2016 In addition, the anti-EMT effects of metformin could be partially in accord with rapamycin, a specific mTOR inhibitor. Metformin 37-46 mechanistic target of rapamycin kinase Homo sapiens 103-107 27599468-12 2016 Although phosphorylation of AMP-activated protein kinase was enhanced by IR and metformin, phosphorylation of mammalian target of rapamycin was enhanced by IR and suppressed by metformin. Metformin 177-186 mechanistic target of rapamycin kinase Homo sapiens 110-139 27600020-3 2016 Pre-incubation of cells with metformin, an AMPK activator, blocked PDGF-induced activation of mTOR and its downstream targets changes of Skp2 and p27 without changing Akt phosphorylation and inhibited ASMCs proliferation. Metformin 29-38 mechanistic target of rapamycin kinase Homo sapiens 94-98 27600020-4 2016 Transfection of ASMCs with AMPK alpha2-specific small interfering RNA (siRNA) reversed the effect of metformin on mTOR phosphorylation, Skp2 and p27 protein expression and cell proliferation. Metformin 101-110 mechanistic target of rapamycin kinase Homo sapiens 114-118 27748082-0 2016 Metformin induces degradation of mTOR protein in breast cancer cells. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 33-37 27748082-8 2016 We show that metformin treatment in MCF-7 breast cancer cells induced degradation of mTOR and sequestration of this protein in a perinuclear region. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 85-89 27654259-8 2016 In parallel, the activation of AMPK and suppression of mTOR seemed to play an important role for the effect of metformin in patients with EC. Metformin 111-120 mechanistic target of rapamycin kinase Homo sapiens 55-59 27283492-1 2016 Metformin displays antileukemic effects partly due to activation of AMPK and subsequent inhibition of mTOR signaling. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 102-106 27362768-5 2016 In addition to the indirect mode of action, metformin may exhibit direct inhibitory effect on cancer cells by targeting mammalian target of rapamycin (mTOR) signaling and anabolic processes. Metformin 44-53 mechanistic target of rapamycin kinase Homo sapiens 120-149 27362768-5 2016 In addition to the indirect mode of action, metformin may exhibit direct inhibitory effect on cancer cells by targeting mammalian target of rapamycin (mTOR) signaling and anabolic processes. Metformin 44-53 mechanistic target of rapamycin kinase Homo sapiens 151-155 27246734-6 2016 Western blot revealed that the expression of Beclin-1 and LC3B-II was enhanced, and the phosphorylation levels of the mammalian target of rapamycin (mTOR) protein and p70S6K were reduced by metformin after SCI. Metformin 190-199 mechanistic target of rapamycin kinase Homo sapiens 118-147 27246734-6 2016 Western blot revealed that the expression of Beclin-1 and LC3B-II was enhanced, and the phosphorylation levels of the mammalian target of rapamycin (mTOR) protein and p70S6K were reduced by metformin after SCI. Metformin 190-199 mechanistic target of rapamycin kinase Homo sapiens 149-153 27246734-9 2016 Hence, metformin attenuated SCI by inhibiting apoptosis and inflammation and enhancing the autophagy via the mTOR/p70S6K signalling pathway. Metformin 7-16 mechanistic target of rapamycin kinase Homo sapiens 109-113 27378194-1 2016 Metformin exerts antitumor effects mainly through AMP-activated protein kinase [AMPK] activation and phosphatidylinositol 3-kinase [PI3K]-Akt-mammalian target of rapamycin [mTOR] inhibition. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 173-177 27223082-1 2016 In this study, we demonstrated that hypoxic conditions stimulated an increase in tunneling nanotube (TNT) formation in chemoresistant ovarian cancer cells (SKOV3, C200).We found that suppressing the mTOR pathway using either everolimus or metformin led to suppression of TNT formation in vitro, verifying TNTs as a potential target for cancer-directed therapy. Metformin 239-248 mechanistic target of rapamycin kinase Homo sapiens 199-203 27391065-3 2016 The anti-diabetic drug metformin has been associated with a decreased cancer prevalence and mortality in several solid tumors, prompting its possible use for ACC treatment.This paper evaluates the in vitro and in vivo anti-cancer effects of metformin using the ACC cell model H295R.Metformin treatment significantly reduces cell viability and proliferation in a dose- and time-dependent manner and associates with a significant inhibition of ERK1/2 and mTOR phosphorylation/activation, as well as with stimulation of AMPK activity. Metformin 23-32 mechanistic target of rapamycin kinase Homo sapiens 453-457 26963096-2 2016 The underlying mechanisms of such phenomenon is related to the effect of metformin on cell proliferation among which, mTOR, AMPK and other targets have been identified. Metformin 73-82 mechanistic target of rapamycin kinase Homo sapiens 118-122 27210058-4 2016 Metformin was reported to be effective against various cancers as it inhibits cell proliferation by activating AMPK, and inhibiting mTOR and HIF-1alpha. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 132-136 27210058-9 2016 Western blot analysis showed marked downregulation of HIF-1alpha and mTOR expression, and upregulation of AMPKalpha in cells treated with metformin and 5-FU combination treatment. Metformin 138-147 mechanistic target of rapamycin kinase Homo sapiens 69-73 27004404-2 2016 Preclinical studies have demonstrated several anticancer molecular mechanisms of metformin including mTOR inhibition, cytotoxic effects, and immunomodulation. Metformin 81-90 mechanistic target of rapamycin kinase Homo sapiens 101-105 27262901-2 2016 An anti-diabetic drug, metformin, has been shown to activate AMP-activated protein kinase (AMPK), which leads to inhibition of mTOR. Metformin 23-32 mechanistic target of rapamycin kinase Homo sapiens 127-131 27262901-3 2016 LAT1 inhibition in combination with metformin could result in more prominent suppression of mTOR activity. Metformin 36-45 mechanistic target of rapamycin kinase Homo sapiens 92-96 26305116-0 2016 Metformin inhibits proliferation and proinflammatory cytokines of human keratinocytes in vitro via mTOR-signaling pathway. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 99-103 26305116-10 2016 Metformin at 50 mM significantly reduced the phosphorylation of mTOR and p70S6K, by 49.0 and 62.1%, respectively. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 64-68 26305116-11 2016 DISCUSSION AND CONCLUSION: Metformin treatment significantly inhibited proliferation and proinflammatory responses in HaCaT cells by a mechanism associated with inhibition of the mTOR signaling pathway. Metformin 27-36 mechanistic target of rapamycin kinase Homo sapiens 179-183 27014780-2 2016 Metformin inhibits mTOR through different mechanisms and may enhance temsirolimus"s antitumor activity. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 19-23 26669511-10 2016 Collectively, these findings establish a clear relationship between cation-selective transporter expression, the AMPK-mTOR-pS6K signaling cascade, and the antiproliferative activity of metformin in breast cancer. Metformin 185-194 mechanistic target of rapamycin kinase Homo sapiens 118-122 26993101-5 2016 Metformin did not affect Akt activation but blocked mTOR phosphorylation in response to PDGF; these were accompanied by the reversion of Skp2 up-regulation and p27 reduction. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 52-56 26892736-3 2016 Anti-tumor metformin action was found to be mediated, at least in part, via activation of adenosine monophosphate-activated protein kinase (AMPK)-intracellular energy sensor, which inhibits the mammalian target of rapamycin (mTOR) and some other signaling pathways. Metformin 11-20 mechanistic target of rapamycin kinase Homo sapiens 194-223 26892736-3 2016 Anti-tumor metformin action was found to be mediated, at least in part, via activation of adenosine monophosphate-activated protein kinase (AMPK)-intracellular energy sensor, which inhibits the mammalian target of rapamycin (mTOR) and some other signaling pathways. Metformin 11-20 mechanistic target of rapamycin kinase Homo sapiens 225-229 26794276-1 2016 BACKGROUND: Preclinical studies in endometrial cancer (EC) show that metformin reduces cellular proliferation by PI3K-AKT-mTOR inhibition. Metformin 69-78 mechanistic target of rapamycin kinase Homo sapiens 122-126 28217402-14 2016 Targeted metabolomics data indicate that mTOR complexes inhibition by Torin 2 reduced glycolytic intermediates and TCA metabolites in HPAF- II and may synergize with metformin to decrease the electron acceptors NAD+ and FAD which may lead to reduced energy production. Metformin 166-175 mechanistic target of rapamycin kinase Homo sapiens 41-45 26893732-3 2016 The anticancer action of metformin involves the enhancement of phosphorylation of liver kinase B1, activation of adenosine monophosphate-activated protein kinase and inhibition of mammalian target of rapamycin, which reduces cell growth. Metformin 25-34 mechanistic target of rapamycin kinase Homo sapiens 180-209 28217402-6 2016 Furthermore, the anti-diabetic drug, metformin, which indirectly inhibits mTOR, has emerged as a potential therapeutic target for PC. Metformin 37-46 mechanistic target of rapamycin kinase Homo sapiens 74-78 28217402-7 2016 The objective of this study is to determine the targeted-metabolomics profile in PDAC cell line (HPAF-II) with mTOR inhibition and the interaction between mTOR ATP-competitive inhibitor (Torin 2) and metformin as potential combined therapy in PC. Metformin 200-209 mechanistic target of rapamycin kinase Homo sapiens 155-159 26967226-6 2016 Additional experiments indicated that metformin increased phosphorylation of AMP-activated protein kinase, which activates autophagy by suppressing mammalian target of rapamycin (mTOR). Metformin 38-47 mechanistic target of rapamycin kinase Homo sapiens 148-177 26967226-6 2016 Additional experiments indicated that metformin increased phosphorylation of AMP-activated protein kinase, which activates autophagy by suppressing mammalian target of rapamycin (mTOR). Metformin 38-47 mechanistic target of rapamycin kinase Homo sapiens 179-183 26505133-0 2015 Metformin synergistically sensitizes FLT3-ITD-positive acute myeloid leukemia to sorafenib by promoting mTOR-mediated apoptosis and autophagy. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 104-108 26496641-1 2016 PURPOSE: Metformin (MF) acts as a tumour-suppressor in renal cell carcinoma (RCC) by inhibiting the AKT/mTOR pathway via AMPK activation. Metformin 9-18 mechanistic target of rapamycin kinase Homo sapiens 104-108 26304716-6 2015 Finally, metformin-mediated AMPK/mTOR/p70S6K was identified as a possible upstream pathway controlling translational regulation of Wee1 and Rad51. Metformin 9-18 mechanistic target of rapamycin kinase Homo sapiens 33-37 26505133-5 2015 Mechanistically, in the presence of metformin, the anticancer potential of sorafenib, accompanying with increased LC3 levels, is found to be synergistically enhanced with the remarkably reduced protein expression of the mTOR/p70S6K/4EBP1 pathway, while not appreciably altering cell cycle. Metformin 36-45 mechanistic target of rapamycin kinase Homo sapiens 220-224 26360050-9 2015 Treatment with metformin inhibited the expression of interleukin (IL)-17, p-STAT3, and p-mTOR. Metformin 15-24 mechanistic target of rapamycin kinase Homo sapiens 89-93 26164004-8 2015 In addition, Western blot showed that metformin activated AMPKalpha at Tyr172, followed by a downregulated phosphorylation of mammalian target of rapamycin (mTOR)/S6 and feedback activation of p-AKT Ser(473) in both OS MG63 cells and CSCs. Metformin 38-47 mechanistic target of rapamycin kinase Homo sapiens 126-155 26164004-8 2015 In addition, Western blot showed that metformin activated AMPKalpha at Tyr172, followed by a downregulated phosphorylation of mammalian target of rapamycin (mTOR)/S6 and feedback activation of p-AKT Ser(473) in both OS MG63 cells and CSCs. Metformin 38-47 mechanistic target of rapamycin kinase Homo sapiens 157-161 26885449-9 2015 Moreover, metformin inhibitory effects were enhanced by mTOR inhibitor suggesting that metformin and mTOR inhibitor utilize distinctive signaling pathways to suppress salivary tumor growth. Metformin 10-19 mechanistic target of rapamycin kinase Homo sapiens 56-60 26885449-9 2015 Moreover, metformin inhibitory effects were enhanced by mTOR inhibitor suggesting that metformin and mTOR inhibitor utilize distinctive signaling pathways to suppress salivary tumor growth. Metformin 10-19 mechanistic target of rapamycin kinase Homo sapiens 101-105 26885449-9 2015 Moreover, metformin inhibitory effects were enhanced by mTOR inhibitor suggesting that metformin and mTOR inhibitor utilize distinctive signaling pathways to suppress salivary tumor growth. Metformin 87-96 mechanistic target of rapamycin kinase Homo sapiens 56-60 26225749-6 2015 Moreover, we demonstrated that AMPK-mTOR signaling played a role in metformin-induced p53 up-regulation. Metformin 68-77 mechanistic target of rapamycin kinase Homo sapiens 36-40 26291325-1 2015 INTRODUCTION: Metformin is proposed as adjuvant therapy in cancer treatment because of its ability to limit cancer incidence by negatively modulating the PI3K/AKT/mTOR pathway. Metformin 14-23 mechanistic target of rapamycin kinase Homo sapiens 163-167 26056043-6 2015 Metformin combined with aspirin significantly inhibited the phosphorylation of mTOR and STAT3, and induced apoptosis as measured by caspase-3 and PARP cleavage. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 79-83 26291325-12 2015 Not only glucose levels but also amino acid concentration can influence the observed metformin inhibitory effect on the mTOR pathway as well as its pro-apoptotic effect. Metformin 85-94 mechanistic target of rapamycin kinase Homo sapiens 120-124 25921843-9 2015 Compared to baseline, metformin significantly improved metabolic parameters and insulin sensitivity, increased SIRT1 gene/protein expression and SIRT1 promoter chromatin accessibility, elevated mTOR gene expression with concomitant reduction in p70S6K phosphorylation in subjects" PBMCs, and modified the plasma N-glycan profile. Metformin 22-31 mechanistic target of rapamycin kinase Homo sapiens 194-198 26050920-11 2015 Metformin influences on AMPK/mTOR cell signaling were evaluated by investigating AKT, AMPK and S6 phosphorylation levels. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 29-33 25854169-5 2015 Cyclin D1 and c-Myc are important regulators of cancer cell growth, and we observed that treatment of thyroid cancer cells with metformin reduced c-Myc and cyclin D1 expression through suppression of mTOR and subsequent inhibition of P70S6K1 and 4E-BP1 phosphorylation. Metformin 128-137 mechanistic target of rapamycin kinase Homo sapiens 200-204 25854169-8 2015 Additionally, knockdown of TSC2, the upstream regulatory molecule of mTOR pathway, or treatment of rapamycin, the mTOR inhibitor, could abolish the effects of metformin to regulate thyroid cancer cell proliferation, migration, EMT, and mTOR pathway molecules. Metformin 159-168 mechanistic target of rapamycin kinase Homo sapiens 69-73 25854169-8 2015 Additionally, knockdown of TSC2, the upstream regulatory molecule of mTOR pathway, or treatment of rapamycin, the mTOR inhibitor, could abolish the effects of metformin to regulate thyroid cancer cell proliferation, migration, EMT, and mTOR pathway molecules. Metformin 159-168 mechanistic target of rapamycin kinase Homo sapiens 114-118 25854169-8 2015 Additionally, knockdown of TSC2, the upstream regulatory molecule of mTOR pathway, or treatment of rapamycin, the mTOR inhibitor, could abolish the effects of metformin to regulate thyroid cancer cell proliferation, migration, EMT, and mTOR pathway molecules. Metformin 159-168 mechanistic target of rapamycin kinase Homo sapiens 114-118 25854169-9 2015 These results indicate that metformin can suppress the proliferation, migration, and EMT of thyroid cancer cell lines by inhibiting mTOR signaling. Metformin 28-37 mechanistic target of rapamycin kinase Homo sapiens 132-136 25854169-0 2015 Metformin inhibits thyroid cancer cell growth, migration, and EMT through the mTOR pathway. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 78-82 25854169-2 2015 Recent evidences have demonstrated that the antidiabetic agent metformin, an activator of 5"-AMP-activated protein kinase, can impair the proliferation and migration of cancer cells via inhibition of mTOR. Metformin 63-72 mechanistic target of rapamycin kinase Homo sapiens 200-204 25854169-4 2015 In this study, we show that metformin can inhibit mTOR pathway to impair growth and migration of the thyroid cancer cell lines. Metformin 28-37 mechanistic target of rapamycin kinase Homo sapiens 50-54 25921843-10 2015 Compared to placebo, metformin increased SIRT1 protein expression and reduced p70S6K phosphorylation (a proxy of mTOR activity). Metformin 21-30 mechanistic target of rapamycin kinase Homo sapiens 113-117 25817233-11 2015 Co-treatment with metformin or AICAR decreased the TNF-alpha-induced intracellular TG, accompanied by significantly enhanced AMPK and ACC phosphorylation, suppressed mTOR and p70S6K phosphorylation, and reduced SREBP-1 and FAS expressions. Metformin 18-27 mechanistic target of rapamycin kinase Homo sapiens 166-170 26111001-5 2015 Mechanistically, we found that metformin inhibited mTOR in all these hepatic tumor cells. Metformin 31-40 mechanistic target of rapamycin kinase Homo sapiens 51-55 26111001-8 2015 Therefore, the various basal autophagy and mTOR activity in different cancer cells may contribute to the controversial findings on the use of metformin in inhibition of cancers in humans. Metformin 142-151 mechanistic target of rapamycin kinase Homo sapiens 43-47 25903858-0 2015 Vitamin D3 potentiates the growth inhibitory effects of metformin in DU145 human prostate cancer cells mediated by AMPK/mTOR signalling pathway. Metformin 56-65 mechanistic target of rapamycin kinase Homo sapiens 120-124 25862373-3 2015 The anti-tumor mechanisms of metformin include activation of the AMP-activated protein kinase/mTOR pathway and direct inhibition of insulin/insulin-like growth factor (IGF)-mediated cellular proliferation. Metformin 29-38 mechanistic target of rapamycin kinase Homo sapiens 94-98 25867026-7 2015 We show that metformin induces decreased proliferation, cell cycle arrest, autophagy, apoptosis and cell death in vitro with a concomitant activation of AMPK, Redd1 and inhibition of the mTOR pathway. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 187-191 26052399-6 2015 Metformin (through 5"-adenosine monophosphate-activated protein kinase pathway activation) and statins (through 3-hydroxy-3-methylglutaryl coenzyme A inhibition) show anti-tumoral properties modifying several steps of RAS/RAF/MEK/ERK, PI3K/AKT/mTOR and Wnt/beta-catenin signaling cascades. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 244-248 25843797-0 2015 DEPTOR-related mTOR suppression is involved in metformin"s anti-cancer action in human liver cancer cells. Metformin 47-56 mechanistic target of rapamycin kinase Homo sapiens 15-19 25843797-2 2015 It is thought that the suppression of mTOR signaling is involved in metformin"s anti-cancer action. Metformin 68-77 mechanistic target of rapamycin kinase Homo sapiens 38-42 25843797-4 2015 In this study, we investigated the mechanism of the suppressing effect of metformin on mTOR signaling and cell proliferation using human liver cancer cells. Metformin 74-83 mechanistic target of rapamycin kinase Homo sapiens 87-91 25843797-5 2015 Metformin suppressed phosphorylation of p70-S6 kinase, and ribosome protein S6, downstream targets of mTOR, and suppressed cell proliferation. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 102-106 25843797-6 2015 We found that DEPTOR, an endogenous substrate of mTOR suppression, is involved in the suppressing effect of metformin on mTOR signaling and cell proliferation in human liver cancer cells. Metformin 108-117 mechanistic target of rapamycin kinase Homo sapiens 49-53 25843797-6 2015 We found that DEPTOR, an endogenous substrate of mTOR suppression, is involved in the suppressing effect of metformin on mTOR signaling and cell proliferation in human liver cancer cells. Metformin 108-117 mechanistic target of rapamycin kinase Homo sapiens 121-125 25843797-7 2015 Metformin increases the protein levels of DEPTOR, intensifies binding to mTOR, and exerts a suppressing effect on mTOR signaling. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 73-77 25843797-7 2015 Metformin increases the protein levels of DEPTOR, intensifies binding to mTOR, and exerts a suppressing effect on mTOR signaling. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 114-118 25843797-8 2015 This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner. Metformin 123-132 mechanistic target of rapamycin kinase Homo sapiens 136-140 25843797-9 2015 Furthermore, metformin exerts a suppressing effect on proteasome activity, DEPTOR-related mTOR signaling, and cell proliferation in an AMPK-dependent manner. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 90-94 25843797-10 2015 We conclude that DEPTOR-related mTOR suppression is involved in metformin"s anti-cancer action in liver, and could be a novel target for anti-cancer therapy. Metformin 64-73 mechanistic target of rapamycin kinase Homo sapiens 32-36 25879666-7 2015 Metformin also markedly decreased serum levels of insulin and reduced insulin resistance, and inhibited phosphorylation of Akt, mammalian target of rapamycin (mTOR), and p70S6 in the liver. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 128-157 25879666-7 2015 Metformin also markedly decreased serum levels of insulin and reduced insulin resistance, and inhibited phosphorylation of Akt, mammalian target of rapamycin (mTOR), and p70S6 in the liver. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 159-163 26045896-10 2015 Moreover, we demonstrate that metformin induces GLUT4 expression and inhibits AR expression and blocks insulin receptor/PI3K/Akt/mTOR signaling in the same hyperplasia human tissues. Metformin 30-39 mechanistic target of rapamycin kinase Homo sapiens 129-133 25661368-7 2015 Furthermore, the mechanisms how metformin sensitized ECa109 cells to IR may be targeting the ATM and AMPK/mTOR/HIF-1alpha pathways. Metformin 32-41 mechanistic target of rapamycin kinase Homo sapiens 106-110 25681087-0 2015 Prevention of tumor growth driven by PIK3CA and HPV oncogenes by targeting mTOR signaling with metformin in oral squamous carcinomas expressing OCT3. Metformin 95-104 mechanistic target of rapamycin kinase Homo sapiens 75-79 25681087-2 2015 We have recently shown that metformin, an oral antidiabetic drug that is also used to treat lipodystrophy in HIV-infected (HIV(+)) individuals, diminishes mTOR activity and prevents the progression of chemically induced experimental HNSCC premalignant lesions. Metformin 28-37 mechanistic target of rapamycin kinase Homo sapiens 155-159 26312913-2 2015 Results from preclinical studies in endometrial cancer show that metformin reduces cellular proliferation by inhibition of the PI3K-AKT-mTOR pathway. Metformin 65-74 mechanistic target of rapamycin kinase Homo sapiens 136-140 26312913-18 2015 We are now exploring the hypothesis that metformin reduces Ki-67 expression by inducing phosphorylation of AMP-activated kinase and subsequent mTOR proproliferative inhibition, independent of insulin and insulin-like growth factor receptor activation. Metformin 41-50 mechanistic target of rapamycin kinase Homo sapiens 143-147 25681087-7 2015 We found that metformin inhibits mTOR signaling and tumor growth in HNSCC cells expressing mutated PIK3CA and HPV oncogenes, and that these activities require the expression of organic cation transporter 3 (OCT3/SLC22A3), a metformin uptake transporter. Metformin 14-23 mechanistic target of rapamycin kinase Homo sapiens 33-37 25503637-8 2014 Agonist induction of AMPK activity with AICAR or metformin increased macroautophagy protein LC3 and normalized p62/SQSTM1 expression and mTOR activity. Metformin 49-58 mechanistic target of rapamycin kinase Homo sapiens 137-141 25417601-9 2015 In conclusion, metformin reduced tumor proliferation in a pre-operative window study in obese EC patients, with dramatic effects on inhibition of the mTOR pathway. Metformin 15-24 mechanistic target of rapamycin kinase Homo sapiens 150-154 25305450-7 2015 Metformin inhibited the expression of insulin growth factor-I receptor (IGF-IR), and phosphatidyl inositol 3-kinase (PI3K), protein kinase B (PKB/AKT) and the downstream mammalian target of rapamycin (mTOR). Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 170-199 25305450-7 2015 Metformin inhibited the expression of insulin growth factor-I receptor (IGF-IR), and phosphatidyl inositol 3-kinase (PI3K), protein kinase B (PKB/AKT) and the downstream mammalian target of rapamycin (mTOR). Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 201-205 25305450-8 2015 IGF-I blocked metformin-induced MM cell apoptosis and reactivation of the PI3K/AKT/mTOR signaling pathway. Metformin 14-23 mechanistic target of rapamycin kinase Homo sapiens 83-87 25305450-10 2015 We conclude that metformin inhibits MM cell proliferation through the IGF-1R/PI3K/AKT/mTOR signaling pathway. Metformin 17-26 mechanistic target of rapamycin kinase Homo sapiens 86-90 25456211-0 2015 AMPK/mTOR-mediated inhibition of survivin partly contributes to metformin-induced apoptosis in human gastric cancer cell. Metformin 64-73 mechanistic target of rapamycin kinase Homo sapiens 5-9 25456211-10 2015 Similarly, forced overexpression of mTOR downstream effector p70S6K1 relieves metformin-induced inhibition of survivin and partly attenuates metformin-induced apoptosis. Metformin 78-87 mechanistic target of rapamycin kinase Homo sapiens 36-40 25456211-10 2015 Similarly, forced overexpression of mTOR downstream effector p70S6K1 relieves metformin-induced inhibition of survivin and partly attenuates metformin-induced apoptosis. Metformin 141-150 mechanistic target of rapamycin kinase Homo sapiens 36-40 25456211-13 2015 Taken together, these evidences suggest that AMPK/mTOR-mediated inhibition of survivin may partly contribute to metformin-induced apoptosis of gastric cancer cell. Metformin 112-121 mechanistic target of rapamycin kinase Homo sapiens 50-54 25310259-7 2014 Metformin targeted the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, suppressed the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and transcriptionally downregulated the expression of multidrug resistance protein 1/P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1). Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 59-88 25310259-8 2014 Collectively, these findings suggested that metformin may target the AMPK/mTOR/HIF-1alpha/P-gp and MRP1 pathways to reverse MDR in hepatocellular carcinoma. Metformin 44-53 mechanistic target of rapamycin kinase Homo sapiens 74-78 25310259-7 2014 Metformin targeted the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, suppressed the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and transcriptionally downregulated the expression of multidrug resistance protein 1/P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1). Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 90-94 25426078-5 2014 Metformin appears to reduce risk for pancreatic cancer and improve survival in diabetics with pancreatic cancer primarily by decreasing insulin/IGF signaling, disrupting mitochondrial respiration, and inhibiting the mammalian target of rapamycin (mTOR) pathway. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 216-245 25426078-5 2014 Metformin appears to reduce risk for pancreatic cancer and improve survival in diabetics with pancreatic cancer primarily by decreasing insulin/IGF signaling, disrupting mitochondrial respiration, and inhibiting the mammalian target of rapamycin (mTOR) pathway. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 247-251 25013215-17 2014 Pre-clinical experiments report that metformin has a growth-static effect on several cancers, including endometrial cancer, which may be partly due to the effect of metformin on the PI3K/AKT/mTOR signal transduction pathway. Metformin 37-46 mechanistic target of rapamycin kinase Homo sapiens 191-195 25013215-17 2014 Pre-clinical experiments report that metformin has a growth-static effect on several cancers, including endometrial cancer, which may be partly due to the effect of metformin on the PI3K/AKT/mTOR signal transduction pathway. Metformin 165-174 mechanistic target of rapamycin kinase Homo sapiens 191-195 25688512-4 2014 Metformin has recently shown some anti-cancer activity in both in vitro and in vivo studies by its indirect properties to decrease insulin and insulin-like growth factor-1 (IGF-1) levels and by its antitumour effect to promote AMPK activation and consequently inhibition to TSC1-2/mTOR complex. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 281-285 25143389-0 2014 Mechanism of metformin-dependent inhibition of mammalian target of rapamycin (mTOR) and Ras activity in pancreatic cancer: role of specificity protein (Sp) transcription factors. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 47-76 25143389-0 2014 Mechanism of metformin-dependent inhibition of mammalian target of rapamycin (mTOR) and Ras activity in pancreatic cancer: role of specificity protein (Sp) transcription factors. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 78-82 25143389-3 2014 Treatment with metformin or down-regulation of Sp TFs by RNAi also inhibits two major pro-oncogenic pathways in pancreatic cancer cells, namely mammalian target of rapamycin (mTOR) signaling and epidermal growth factor (EGFR)-dependent activation of Ras. Metformin 15-24 mechanistic target of rapamycin kinase Homo sapiens 144-173 25143389-3 2014 Treatment with metformin or down-regulation of Sp TFs by RNAi also inhibits two major pro-oncogenic pathways in pancreatic cancer cells, namely mammalian target of rapamycin (mTOR) signaling and epidermal growth factor (EGFR)-dependent activation of Ras. Metformin 15-24 mechanistic target of rapamycin kinase Homo sapiens 175-179 25143389-4 2014 Metformin and Sp knockdown by RNAi decreased expression of the insulin-like growth factor-1 receptor (IGF-1R), resulting in inhibition of mTOR signaling. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 138-142 25143389-6 2014 Thus, the antineoplastic activities of metformin in pancreatic cancer are due, in part, to down-regulation of Sp TFs and Sp-regulated IGF-1R and EGFR, which in turn results in inhibition of mTOR and Ras signaling, respectively. Metformin 39-48 mechanistic target of rapamycin kinase Homo sapiens 190-194 24714080-0 2014 Metformin sensitizes human bladder cancer cells to TRAIL-induced apoptosis through mTOR/S6K1-mediated downregulation of c-FLIP. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 83-87 24714080-8 2014 Taken together, our results indicate that metformin sensitizes human bladder cancer cells to TRAIL-induced apoptosis through downregulation of c-FLIP, which is mediated by the mTOR/S6K1 pathway, but independent of AMPK; furthermore, these findings provide a rationale for the combined application of metformin with TRAIL in the treatment of bladder cancer. Metformin 42-51 mechanistic target of rapamycin kinase Homo sapiens 176-180 25254953-11 2014 Additionally, under low glucose conditions metformin significantly decreased phosphorylation of AKT and various targets of mTOR, while phospho-AMPK was not significantly altered. Metformin 43-52 mechanistic target of rapamycin kinase Homo sapiens 123-127 25295009-7 2014 This article highlights the central role of the mechanistic target of rapamycin (mTOR) in mediating crosstalk between insulin/IGF-1 and GPCR signaling in pancreatic cancer cells and proposes strategies, including the use of metformin, to target this signaling system in PDAC cells. Metformin 224-233 mechanistic target of rapamycin kinase Homo sapiens 48-79 25295009-7 2014 This article highlights the central role of the mechanistic target of rapamycin (mTOR) in mediating crosstalk between insulin/IGF-1 and GPCR signaling in pancreatic cancer cells and proposes strategies, including the use of metformin, to target this signaling system in PDAC cells. Metformin 224-233 mechanistic target of rapamycin kinase Homo sapiens 81-85 24714080-6 2014 However, metformin inhibited the mTOR/S6K1 pathway in 253J and RT4 cells, which usually regulates protein translation; moreover, knockdown of S6K1 effectively reduced the levels of c-FLIPL, indicating that metformin downregulates c-FLIP through inhibition of the mTOR/S6K1 pathway. Metformin 9-18 mechanistic target of rapamycin kinase Homo sapiens 33-37 24714080-6 2014 However, metformin inhibited the mTOR/S6K1 pathway in 253J and RT4 cells, which usually regulates protein translation; moreover, knockdown of S6K1 effectively reduced the levels of c-FLIPL, indicating that metformin downregulates c-FLIP through inhibition of the mTOR/S6K1 pathway. Metformin 9-18 mechanistic target of rapamycin kinase Homo sapiens 263-267 24714080-6 2014 However, metformin inhibited the mTOR/S6K1 pathway in 253J and RT4 cells, which usually regulates protein translation; moreover, knockdown of S6K1 effectively reduced the levels of c-FLIPL, indicating that metformin downregulates c-FLIP through inhibition of the mTOR/S6K1 pathway. Metformin 206-215 mechanistic target of rapamycin kinase Homo sapiens 33-37 24859412-0 2014 Metformin sensitizes chemotherapy by targeting cancer stem cells and the mTOR pathway in esophageal cancer. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 73-77 24859412-9 2014 Immunoblots and transcriptional analyses further confirm that metformin downregulated these CSC-related genes and the components of the mTOR pathway in a dose-dependent manner. Metformin 62-71 mechanistic target of rapamycin kinase Homo sapiens 136-140 24859412-12 2014 Metformin inhibits EC cell growth and sensitizes EC cells to 5-FU cytotoxic effects by targeting CSCs and the components of mTOR. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 124-128 24943970-3 2014 It is suggested that metformin has an anticancer and antiproliferative effect and affects the apoptosis by activating the AMPK and inhibiting the mammalian target of rapamycin (mTOR). Metformin 21-30 mechanistic target of rapamycin kinase Homo sapiens 146-175 25076330-6 2014 Metformin is proposed to target metabolic pathways involved in tumorigenesis, specifically the AMPK-mTOR complex. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 100-104 25642303-5 2014 When MKN-45 cells were treated with metformin/cisplatin, the expression of survivin and mTOR were increased. Metformin 36-45 mechanistic target of rapamycin kinase Homo sapiens 88-92 24193408-8 2014 Interestingly, combining low concentrations of rapamycin and metformin was more effective for inhibiting mTOR complex 1 activity in TRPP1-deficient cells than either drug alone. Metformin 61-70 mechanistic target of rapamycin kinase Homo sapiens 105-109 25642303-6 2014 The antagonistic effect of metformin on cisplatin could be through survivin and mTOR signaling pathways. Metformin 27-36 mechanistic target of rapamycin kinase Homo sapiens 80-84 24943970-3 2014 It is suggested that metformin has an anticancer and antiproliferative effect and affects the apoptosis by activating the AMPK and inhibiting the mammalian target of rapamycin (mTOR). Metformin 21-30 mechanistic target of rapamycin kinase Homo sapiens 177-181 24788596-5 2014 Furthermore, metformin sensitized ICC cells to certain chemotherapeutic agents, such as sorafenib, 5-fluorouracil and As2O3 by targeting the AMPK/mTOR/HIF-1alpha/MRP1 pathway and ERK. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 146-150 24940426-2 2014 The mechanism of action of metformin involves regulation of the adenosine monophosphate-activated protein kinase/mammalian target of rapamycin signaling pathway, which is implicated in the control of protein synthesis and cell proliferation. Metformin 27-36 mechanistic target of rapamycin kinase Homo sapiens 113-142 24810045-0 2014 Metformin lowers Ser-129 phosphorylated alpha-synuclein levels via mTOR-dependent protein phosphatase 2A activation. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 67-71 24810045-6 2014 On the other hand, metformin-induced phospho-Ser129 alpha-synuclein reduction was consistently associated with inhibition of mammalian target of rapamycin (mTOR) and activation of protein phosphatase 2A (PP2A). Metformin 19-28 mechanistic target of rapamycin kinase Homo sapiens 125-154 24810045-6 2014 On the other hand, metformin-induced phospho-Ser129 alpha-synuclein reduction was consistently associated with inhibition of mammalian target of rapamycin (mTOR) and activation of protein phosphatase 2A (PP2A). Metformin 19-28 mechanistic target of rapamycin kinase Homo sapiens 156-160 24520038-0 2014 Repurposing of metformin and aspirin by targeting AMPK-mTOR and inflammation for pancreatic cancer prevention and treatment. Metformin 15-24 mechanistic target of rapamycin kinase Homo sapiens 55-59 24764656-13 2014 New players in mTOR signaling pathway, such as non-steroidal anti-inflammatory drug and metformin with therapeutic potentials are also discussed here. Metformin 88-97 mechanistic target of rapamycin kinase Homo sapiens 15-19 24534455-10 2014 Moreover, both statins and metformin are known to inhibit mTOR via AMPK activation so that they would fully exploit the beneficial effects of mTOR inhibition in atherosclerosis. Metformin 27-36 mechanistic target of rapamycin kinase Homo sapiens 58-62 24534455-10 2014 Moreover, both statins and metformin are known to inhibit mTOR via AMPK activation so that they would fully exploit the beneficial effects of mTOR inhibition in atherosclerosis. Metformin 27-36 mechanistic target of rapamycin kinase Homo sapiens 142-146 24520038-6 2014 For metformin, the most important mechanism may involve the inhibition of mTOR signaling via AMP-activated protein kinase (AMPK)-dependent and -independent pathways. Metformin 4-13 mechanistic target of rapamycin kinase Homo sapiens 74-78 24437490-9 2014 Moreover, metformin blocked membrane-initiated signals of AR to the mammalian target of rapamycin/p70S6Kinase pathway by inhibiting AR phosphorylation and its association with c-Src. Metformin 10-19 mechanistic target of rapamycin kinase Homo sapiens 68-97 26351208-2 2014 Adenosine 5"-monophosphate-activated protein kinase (AMPK) activators such as metformin have similar actions in keeping with the TSC2/1 pathway linking activation of AMPK to inhibition of mTOR. Metformin 78-87 mechanistic target of rapamycin kinase Homo sapiens 188-192 24612549-9 2014 In addition, these tamoxifen-induced effects that were enhanced by metformin may be involved in the bax/bcl-2 apoptotic pathway and the AMPK/mTOR/p70S6 growth pathway. Metformin 67-76 mechanistic target of rapamycin kinase Homo sapiens 141-145 24322659-8 2014 Molecular analysis indicated that metformin induced downregulation of ErbB2 and EGFR expression and inhibited the phosphorylation of ErbB family members, insulin-like growth factor-1R, AKT, mTOR, and STAT3 in vivo. Metformin 34-43 mechanistic target of rapamycin kinase Homo sapiens 190-194 24474794-9 2014 Metformin directly inhibited mTOR by enhancing PRAS40"s association with RAPTOR, whereas AICAR blocked the cell cycle through proteasomal degradation of the G2M phosphatase cdc25c. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 29-33 24750786-3 2014 Metformin exerts anticancer effects by primarily blocking the pivotal LKB1/AMPK/mTOR/S6K1 pathway-dependent cell growth, induces selective lethal effects on GSC by impairing the GSC-initiating spherogenesis and inhibits the proliferation of CD133+ cells, while having a low or null effect on differentiated glioblastoma cells and normal human stem cells. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 80-84 24420540-5 2014 Administration of metformin was equally effective in attenuating transverse aortic constriction-induced LV remodeling in both wild-type and AMPKalpha2 knockout mice, as evidenced by reduced LV and lung weights, a preserved LV ejection fraction, and reduced phosphorylation of mammalian target of rapamycin (p-mTOR(Ser2448)) and its downstream target p-p70S6K(Thr389). Metformin 18-27 mechanistic target of rapamycin kinase Homo sapiens 276-305 24420540-5 2014 Administration of metformin was equally effective in attenuating transverse aortic constriction-induced LV remodeling in both wild-type and AMPKalpha2 knockout mice, as evidenced by reduced LV and lung weights, a preserved LV ejection fraction, and reduced phosphorylation of mammalian target of rapamycin (p-mTOR(Ser2448)) and its downstream target p-p70S6K(Thr389). Metformin 18-27 mechanistic target of rapamycin kinase Homo sapiens 309-313 24505341-8 2014 Metformin has been reported to activate AMPK, thereby suppressing mTOR, which plays an important role for protein synthesis, cell cycle progression, and cell survival. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 66-70 24505341-10 2014 Furthermore, hyperthermia potentiated the effect of metformin to activate AMPK and inactivate mTOR and S6K. Metformin 52-61 mechanistic target of rapamycin kinase Homo sapiens 94-98 24505341-11 2014 Cell proliferation was markedly suppressed by metformin or combination of metformin and hyperthermia, which could be attributed to activation of AMPK leading to inactivation of mTOR. Metformin 46-55 mechanistic target of rapamycin kinase Homo sapiens 177-181 24505341-11 2014 Cell proliferation was markedly suppressed by metformin or combination of metformin and hyperthermia, which could be attributed to activation of AMPK leading to inactivation of mTOR. Metformin 74-83 mechanistic target of rapamycin kinase Homo sapiens 177-181 26464852-4 2014 Here we investigated the effect of metformin and rapamycin on mTOR-related phenotypes in cell lines of epithelial origin. Metformin 35-44 mechanistic target of rapamycin kinase Homo sapiens 62-66 26464852-8 2014 However, the inhibition of the mTOR pathway by rapamycin did not have a negative effect on p21 expression, suggesting that metformin regulates p21 upstream of mTOR. Metformin 123-132 mechanistic target of rapamycin kinase Homo sapiens 31-35 26464852-8 2014 However, the inhibition of the mTOR pathway by rapamycin did not have a negative effect on p21 expression, suggesting that metformin regulates p21 upstream of mTOR. Metformin 123-132 mechanistic target of rapamycin kinase Homo sapiens 159-163 24351837-5 2013 Further experiments revealed that metformin activated AMP-activated protein kinase (AMPK) and suppressed mammalian target of rapamycin (mTOR), the central regulator of protein synthesis and cell growth. Metformin 34-43 mechanistic target of rapamycin kinase Homo sapiens 105-134 24351837-5 2013 Further experiments revealed that metformin activated AMP-activated protein kinase (AMPK) and suppressed mammalian target of rapamycin (mTOR), the central regulator of protein synthesis and cell growth. Metformin 34-43 mechanistic target of rapamycin kinase Homo sapiens 136-140 24351837-6 2013 Moreover, daily treatment of metformin led to a substantial inhibition of tumor growth in a xenograft model with concomitant decrease in the expression of proliferating cell nuclear antigen (PCNA), cyclin D1 and p-mTOR. Metformin 29-38 mechanistic target of rapamycin kinase Homo sapiens 214-218 23408390-3 2013 Metformin, which represses mTOR signaling by activating adenosine monophosphate-activated protein kinase, has been shown to decrease liver carcinogenesis in population studies. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 27-31 24180199-6 2013 Metformin may exert its anti-cancer activity by a direct effect (insulin) and an indirect effect (AMPK and mTOR). Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 107-111 24009772-5 2013 Additionally rapamycin, a known inhibitor of mTOR-dependent protein synthesis, rescued cells from metformin-induced apoptosis and down-regulated CHOP expression. Metformin 98-107 mechanistic target of rapamycin kinase Homo sapiens 45-49 23526220-11 2013 This is the first study to demonstrate that metformin suppresses STAT3 activation via LKB1-AMPK-mTOR-independent but ROS-related and autocrine IL-6 production-related pathways. Metformin 44-53 mechanistic target of rapamycin kinase Homo sapiens 96-100 23845075-8 2013 Metformin activates 5-adenosine monophosphate-activated protein kinase (AMPK), that has growth inhibition effects on human cancer cell lines via inhibition of its downstream target mammalian target of rapamycin (mTOR), and decreases the expression of Livin, a protein involved in both cell proliferation and survivalexpressed at high level in neoplastic cell. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 181-210 23845075-8 2013 Metformin activates 5-adenosine monophosphate-activated protein kinase (AMPK), that has growth inhibition effects on human cancer cell lines via inhibition of its downstream target mammalian target of rapamycin (mTOR), and decreases the expression of Livin, a protein involved in both cell proliferation and survivalexpressed at high level in neoplastic cell. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 212-216 23891275-9 2013 FRAP concentrations increased significantly with metformin (p=0.012). Metformin 49-58 mechanistic target of rapamycin kinase Homo sapiens 0-4 23986086-3 2013 The anti-diabetic drug metformin is a stereotypical DR mimetic that exerts its anti-cancer activity through a dual mechanism involving insulin-related (systemic) and mTOR-related (cell-autonomous) effects. Metformin 23-32 mechanistic target of rapamycin kinase Homo sapiens 166-170 23880192-1 2013 OBJECTIVES: Metformin impairs endothelialization of drug eluting stents (DES) due to convergent signaling at the mammalian target of rapamycin (mTOR) pathway. Metformin 12-21 mechanistic target of rapamycin kinase Homo sapiens 113-142 23880192-1 2013 OBJECTIVES: Metformin impairs endothelialization of drug eluting stents (DES) due to convergent signaling at the mammalian target of rapamycin (mTOR) pathway. Metformin 12-21 mechanistic target of rapamycin kinase Homo sapiens 144-148 23525940-1 2012 The gerosuppressant metformin operates as an efficient inhibitor of the mTOR/S6K1 gerogenic pathway due to its ability to ultimately activate the energy-sensor AMPK. Metformin 20-29 mechanistic target of rapamycin kinase Homo sapiens 72-76 23922888-10 2013 As reported, metformin activated AMP-activated protein kinase (AMPK) through phosphorylation; however its inhibitory effect on the mammalian target of rapamycin (mTOR) pathway did not necessarily correlate with its anti-tumor activity toward EpCAM(+) tumor-initiating HCC cells. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 131-160 23922888-10 2013 As reported, metformin activated AMP-activated protein kinase (AMPK) through phosphorylation; however its inhibitory effect on the mammalian target of rapamycin (mTOR) pathway did not necessarily correlate with its anti-tumor activity toward EpCAM(+) tumor-initiating HCC cells. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 162-166 23922888-11 2013 These results indicate that metformin is a promising therapeutic agent for the elimination of tumor-initiating HCC cells and suggest as-yet-unknown functions other than its inhibitory effect on the AMPK/mTOR pathway. Metformin 28-37 mechanistic target of rapamycin kinase Homo sapiens 203-207 23632475-4 2013 Metformin (i) activated the ataxia telengiectasia-mutated (ATM)-AMPK-p53/p21(cip1) and inhibited the Akt-mammalian target of rapamycin (mTOR)-eIF4E-binding protein 1 (4EBP1) pathways, (ii) induced G1 cycle arrest and (iii) enhanced apoptosis. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 101-134 23632475-4 2013 Metformin (i) activated the ataxia telengiectasia-mutated (ATM)-AMPK-p53/p21(cip1) and inhibited the Akt-mammalian target of rapamycin (mTOR)-eIF4E-binding protein 1 (4EBP1) pathways, (ii) induced G1 cycle arrest and (iii) enhanced apoptosis. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 136-140 23686371-5 2013 We observed an association between G6P accumulation, mTOR activation, endoplasmic reticulum (ER) stress, and impaired contractile function, all of which were prevented by pretreating animals with rapamycin (mTOR inhibition) or metformin (AMPK activation). Metformin 227-236 mechanistic target of rapamycin kinase Homo sapiens 53-57 22721394-6 2013 As metformin may act as an anticancer drug through inhibition of mTOR, it might have greater benefice than suggested by insulin lowering alone. Metformin 3-12 mechanistic target of rapamycin kinase Homo sapiens 65-69 23589723-5 2013 Furthermore, cotreatment of CB-PIC and metformin enhanced the inhibition of HIF1 alpha and Akt/mTOR and the activation of AMPK alpha and pACC in hypoxic SW620 cells. Metformin 39-48 mechanistic target of rapamycin kinase Homo sapiens 95-99 23437362-9 2013 Metformin induced a more pronounced inhibition of proliferation than either KU63794 or rapamycin while, the active-site mTOR inhibitor was more effective than rapamycin. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 120-124 23879009-7 2013 It can therefore be concluded that metformin as an inhibitor of mTOR may be a factor that suppresses tumor development. Metformin 35-44 mechanistic target of rapamycin kinase Homo sapiens 64-68 23667692-8 2013 Metformin was associated with a reduction of phospho-Erk and phospho-mTOR independent of Akt and AMPK phosphorylation. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 69-73 22963881-10 2013 Comparing the two groups in a final multivariate model, AOPP, FRAP, and AGE levels changed more significantly in metformin compared with lifestyle modification alone (p = 0.007, p < 0.001 and p < 0.001 respectively). Metformin 113-122 mechanistic target of rapamycin kinase Homo sapiens 62-66 23449430-0 2013 Metformin impairs vascular endothelial recovery after stent placement in the setting of locally eluted mammalian target of rapamycin inhibitors via S6 kinase-dependent inhibition of cell proliferation. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 103-132 21676631-8 2013 Further study revealed metformin induced the activation of AMP-activated protein kinase (AMPK), and inhibited mammalian target of rapamycin (mTOR), which is a central regulator of protein synthesis and cell growth, and negatively regulated by AMPK. Metformin 23-32 mechanistic target of rapamycin kinase Homo sapiens 110-139 21676631-8 2013 Further study revealed metformin induced the activation of AMP-activated protein kinase (AMPK), and inhibited mammalian target of rapamycin (mTOR), which is a central regulator of protein synthesis and cell growth, and negatively regulated by AMPK. Metformin 23-32 mechanistic target of rapamycin kinase Homo sapiens 141-145 24335168-4 2013 Treatment with metformin was also associated with activation of AMP kinase and inhibition of mTOR/p70S6K/pS6 signaling in both cells. Metformin 15-24 mechanistic target of rapamycin kinase Homo sapiens 93-97 22659796-6 2012 Human insulin and analogs activated AKT/mTOR signaling and stimulated ALL cell proliferation (as measured by flow cytometric methods), but metformin and rosiglitazone blocked AKT/mTOR signaling and inhibited proliferation. Metformin 139-148 mechanistic target of rapamycin kinase Homo sapiens 179-183 22735790-7 2012 Analyzing the expression status and the integrity of LKB1-AMPK-mTOR signaling, we found that cervical cancer cells sensitive to metformin were LKB1 intact and exerted an integral AMPK-mTOR signaling response after the treatment. Metformin 128-137 mechanistic target of rapamycin kinase Homo sapiens 63-67 22735790-7 2012 Analyzing the expression status and the integrity of LKB1-AMPK-mTOR signaling, we found that cervical cancer cells sensitive to metformin were LKB1 intact and exerted an integral AMPK-mTOR signaling response after the treatment. Metformin 128-137 mechanistic target of rapamycin kinase Homo sapiens 184-188 22540890-0 2012 Metformin, an antidiabetic agent reduces growth of cutaneous squamous cell carcinoma by targeting mTOR signaling pathway. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 98-102 22540890-5 2012 The mechanism by which metformin manifests antitumor effects appears to be dependent on the inhibition of nuclear factor kappa B (NFkB) and mTOR signaling pathways. Metformin 23-32 mechanistic target of rapamycin kinase Homo sapiens 140-144 22540890-10 2012 These results suggest that metformin blocks SCC growth by dampening NFkB and mTOR signaling pathways. Metformin 27-36 mechanistic target of rapamycin kinase Homo sapiens 77-81 23151022-10 2012 Metformin induced an apparent cell cycle arrest at the G0/G1 phase, which was accompanied by an obvious activation of the AMP kinase pathway and a strongly decreased activation of mammalian target of rapamycin and S6 kinase. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 180-209 22406476-12 2012 Aspirin and metformin (an activator of AMPK) increased inhibition of mTOR and Akt, as well as autophagy in CRC cells. Metformin 12-21 mechanistic target of rapamycin kinase Homo sapiens 69-73 22611195-3 2012 We provide a unique genome-wide analysis of translational targets of canonical mTOR inhibitors (rapamycin and PP242) compared with metformin, revealing that metformin controls gene expression at the level of mRNA translation to an extent comparable to that of canonical mTOR inhibitors. Metformin 157-166 mechanistic target of rapamycin kinase Homo sapiens 79-83 22611195-3 2012 We provide a unique genome-wide analysis of translational targets of canonical mTOR inhibitors (rapamycin and PP242) compared with metformin, revealing that metformin controls gene expression at the level of mRNA translation to an extent comparable to that of canonical mTOR inhibitors. Metformin 157-166 mechanistic target of rapamycin kinase Homo sapiens 270-274 22389381-2 2012 Recent studies showed that the antidiabetic agent metformin decreases proliferation of cancer cells through 5"-AMP-activated protein kinase (AMPK)-dependent inhibition of mTOR. Metformin 50-59 mechanistic target of rapamycin kinase Homo sapiens 171-175 22469973-0 2012 Luteinizing hormone facilitates angiogenesis in ovarian epithelial tumor cells and metformin inhibits the effect through the mTOR signaling pathway. Metformin 95-104 mechanistic target of rapamycin kinase Homo sapiens 137-141 22469973-7 2012 However, metformin inhibited the mTOR signaling pathway and further blocked LH-induced VEGF and slit2 expression. Metformin 9-18 mechanistic target of rapamycin kinase Homo sapiens 33-37 22469973-9 2012 However, metformin could inhibit tumor angiogenesis by blocking the mTOR signaling pathway. Metformin 9-18 mechanistic target of rapamycin kinase Homo sapiens 68-72 22389381-7 2012 Treatment with metformin was associated with inhibition of mTOR/p70S6K/pS6 signaling and downregulation of pERK in both TT and MZ-CRC-1 cells. Metformin 15-24 mechanistic target of rapamycin kinase Homo sapiens 59-63 22378068-0 2012 Therapeutic metformin/AMPK activation blocked lymphoma cell growth via inhibition of mTOR pathway and induction of autophagy. Metformin 12-21 mechanistic target of rapamycin kinase Homo sapiens 85-89 22252099-0 2012 Metformin potentiates the effects of paclitaxel in endometrial cancer cells through inhibition of cell proliferation and modulation of the mTOR pathway. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 139-143 22252099-6 2012 Western immunoblotting was performed to determine the effect of metformin/paclitaxel on the mTOR pathway. Metformin 64-73 mechanistic target of rapamycin kinase Homo sapiens 92-96 22252099-15 2012 CONCLUSIONS: Metformin potentiates the effects of paclitaxel in endometrial cancer cells through inhibition of cell proliferation and modulation of the mTOR pathway. Metformin 13-22 mechanistic target of rapamycin kinase Homo sapiens 152-156 22593441-4 2012 Therefore, simultaneously targeting AMPK through metformin and the PI3K/AKT/mTOR pathway by an mTOR inhibitor could become a therapeutic approach. Metformin 49-58 mechanistic target of rapamycin kinase Homo sapiens 95-99 22443173-12 2012 Metformin activates AMPK, which inhibits the mammalian target of rapamycin (mTOR) pathway. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 45-74 22443173-12 2012 Metformin activates AMPK, which inhibits the mammalian target of rapamycin (mTOR) pathway. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 76-80 22378068-5 2012 Metformin-induced AMPK activation was associated with the inhibition of the mTOR signaling without involving AKT. Metformin 0-9 mechanistic target of rapamycin kinase Homo sapiens 76-80 22378068-6 2012 Moreover, lymphoma cell response to the chemotherapeutic agent doxorubicin and mTOR inhibitor temsirolimus was significantly enhanced when co-treated with metformin. Metformin 155-164 mechanistic target of rapamycin kinase Homo sapiens 79-83