PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 33915902-9 2021 In addition, metformin treatment increased the expression of monophosphate (AMP)-activated protein kinase (AMPK) and p53 in both HCT116 xenografts and colorectal cancer cell lines and decreased the expression of the urea cycle enzymes, including carbamoyl phosphate synthase 1 (CPS1), arginase 1 (ARG1), ornithine trans-carbamylase (OTC), and ODC. Metformin 13-22 tumor protein p53 Homo sapiens 117-120 33350292-0 2021 Metformin promotes apoptosis in primary breast cancer cells by downregulation of cyclin D1 and upregulation of P53 through an AMPK-alpha independent mechanism. Metformin 0-9 tumor protein p53 Homo sapiens 111-114 33350292-1 2021 AIM: In the present study we aimed to figure out the effect of metformin on the expression of AMPK-alpha, cyclin D1 and Tp53, and apoptosis in primary breast cancer cells (PBCCs). Metformin 63-72 tumor protein p53 Homo sapiens 120-124 33350292-8 2021 25mM dose of metformin increased p53 expression significantly compared with the non-treated group. Metformin 13-22 tumor protein p53 Homo sapiens 33-36 33350292-10 2021 CONCLUSION: Metformin can modulate cyclin D1 and p53 expression through AMPK-alpha independent mechanism in breast cancer cells, leading to cell proliferation inhibition and apoptosis induction. Metformin 12-21 tumor protein p53 Homo sapiens 49-52 33358075-9 2021 Metformin has been demonstrated to reduce cell-viability post-radiotherapy in both rectal and prostate cancer cell lines, with an enhanced effect in tumours with a p53 mutation and increased apoptosis post-radiotherapy for cervical cancer. Metformin 0-9 tumor protein p53 Homo sapiens 164-167 33915902-11 2021 These results demonstrate that metformin inhibited CRC cell proliferation via activating AMPK/p53 and that there was an association between metformin, urea cycle inhibition and a reduction in putrescine generation. Metformin 31-40 tumor protein p53 Homo sapiens 94-97 33191800-5 2021 Metformin treatment was negatively associated with p53-AP in T2DM patients. Metformin 0-9 tumor protein p53 Homo sapiens 51-54 33149857-9 2020 Generally, metabolic memory increased p53 and acetyl-P53 and decreased SIRT1 proteins in HUVECs, which were reversed by alpha-mangostin and metformin. Metformin 140-149 tumor protein p53 Homo sapiens 38-41 33187870-10 2021 Metformin treatment reverted LMNA, LMNC, and p53 expression levels to normal levels. Metformin 0-9 tumor protein p53 Homo sapiens 45-48 33051086-0 2020 Metformin inhibits the inflammatory and oxidative stress response induced by skin UVB-irradiation and provides 4-hydroxy-2-nonenal and nitrotyrosine formation and p53 protein activation. Metformin 0-9 tumor protein p53 Homo sapiens 163-166 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 tumor protein p53 Homo sapiens 130-133 32742376-5 2020 In HCT116 cells expressing wild-type (wt) TP53, SIRT inhibitors were found to act antagonistically with multiple chemotherapeutic agents (cisplatin, 5-fluorouracil, oxaliplatin, gefitinib, LY294002 and metformin), and decreased the anti-tumor effects of these agents. Metformin 202-211 tumor protein p53 Homo sapiens 42-46 32869837-0 2020 Metformin inhibits the growth of ovarian cancer cells by promoting the Parkin-induced p53 ubiquitination. Metformin 0-9 tumor protein p53 Homo sapiens 86-89 32869837-10 2020 Further, up-regulated Parkin expression promoted the ubiquitination and degradation of p53, and metformin inhibited the expression of p53 to suppress the proliferation of chemo-resistant ovarian cancer cells. Metformin 96-105 tumor protein p53 Homo sapiens 134-137 32869837-11 2020 Mechanistically, metformin could inhibit the growth of ovarian cancer cells by promoting the Parkin-induced p53 ubiquitination. Metformin 17-26 tumor protein p53 Homo sapiens 108-111 32869837-12 2020 Altogether, our study demonstrated an inhibitory role of metformin in the growth of chemo-resistant cancer cells through promoting the Parkin-induced p53 ubiquitination, which provides a novel mechanism of metformin for treating ovarian cancer. Metformin 57-66 tumor protein p53 Homo sapiens 150-153 32869837-12 2020 Altogether, our study demonstrated an inhibitory role of metformin in the growth of chemo-resistant cancer cells through promoting the Parkin-induced p53 ubiquitination, which provides a novel mechanism of metformin for treating ovarian cancer. Metformin 206-215 tumor protein p53 Homo sapiens 150-153 31047842-12 2019 Upon restoration of WT-TP53 activity in MIA-PaCa-2 cells, an altered sensitivity to the combination of certain NAX compounds and metformin was observed compared to the parental cells which normally lack WT-TP53. Metformin 129-138 tumor protein p53 Homo sapiens 23-27 32606605-0 2020 Metformin Decreases Insulin Resistance in Type 1 Diabetes Through Regulating p53 and RAP2A in vitro and in vivo. Metformin 0-9 tumor protein p53 Homo sapiens 77-80 32606605-8 2020 Metformin could effectively improve insulin resistance and inflammatory response while down-regulating p53 and up-regulating RAP2A. Metformin 0-9 tumor protein p53 Homo sapiens 103-106 32606605-10 2020 Conclusion: Metformin improves T1D insulin resistance and inflammatory response through p53/RAP2A pathway, and the regulation of p53/RAP2A pathway is conducive to improving the efficacy of metformin in the treatment of insulin resistance. Metformin 12-21 tumor protein p53 Homo sapiens 88-91 32606605-10 2020 Conclusion: Metformin improves T1D insulin resistance and inflammatory response through p53/RAP2A pathway, and the regulation of p53/RAP2A pathway is conducive to improving the efficacy of metformin in the treatment of insulin resistance. Metformin 189-198 tumor protein p53 Homo sapiens 129-132 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 tumor protein p53 Homo sapiens 205-208 32631421-11 2020 In addition, metformin upregulated the expression of DDR-1 and p53 in human cervical cancer cells. Metformin 13-22 tumor protein p53 Homo sapiens 63-66 31047842-12 2019 Upon restoration of WT-TP53 activity in MIA-PaCa-2 cells, an altered sensitivity to the combination of certain NAX compounds and metformin was observed compared to the parental cells which normally lack WT-TP53. Metformin 129-138 tumor protein p53 Homo sapiens 206-210 31258748-0 2019 Role of p53 Family Proteins in Metformin Anti-Cancer Activities. Metformin 31-40 tumor protein p53 Homo sapiens 8-11 31244286-0 2019 Metformin Modulates Cyclin D1 and P53 Expression to Inhibit Cell Proliferation and to Induce Apoptosis in Cervical Cancer Cell Lines. Metformin 0-9 tumor protein p53 Homo sapiens 34-37 31244286-12 2019 Moreover, 30 mM or higher doses of metformin increase significantly p53 expression (p< 0.001). Metformin 35-44 tumor protein p53 Homo sapiens 68-71 31244286-14 2019 Conclusion: Metformin can modulate cyclin D1 and p53 expression in HeLa cancer cell line, leadingto inhibition of cell proliferation and induction of apoptosis. Metformin 12-21 tumor protein p53 Homo sapiens 49-52 31258748-7 2019 We also aimed to discuss the role of p53 family proteins in metformin-mediated suppression of cancer growth and survival. Metformin 60-69 tumor protein p53 Homo sapiens 37-40 31091555-11 2019 Metformin stimulates p53- and AMPK-dependent pathways whereas CO can selectively trigger the PERK-dependent signaling pathway. Metformin 0-9 tumor protein p53 Homo sapiens 21-24 31114366-4 2019 Metformin can activate p53 by activating AMPK and thereby ultimately stop the cell cycle. Metformin 0-9 tumor protein p53 Homo sapiens 23-26 30098371-7 2018 In our project we aim to understand the effects of metformin on p53 and DNA-BER system based on the oxidative status in type 2 diabetes patients. Metformin 51-60 tumor protein p53 Homo sapiens 64-67 30710424-9 2019 The marked reduction in SIRT1 expression by combination of metformin and tenovin-6 increased acetylation of p53 at lysine 382 and enhanced p53 stability in LKB1-deficient A549 cells. Metformin 59-68 tumor protein p53 Homo sapiens 108-111 30710424-9 2019 The marked reduction in SIRT1 expression by combination of metformin and tenovin-6 increased acetylation of p53 at lysine 382 and enhanced p53 stability in LKB1-deficient A549 cells. Metformin 59-68 tumor protein p53 Homo sapiens 139-142 30866414-7 2019 Moreover, we showed that p53 family member DeltaNp63alpha transcriptionally suppressed integrin beta1 expression and is responsible for metformin-mediated upregulation of integrin beta1. Metformin 136-145 tumor protein p53 Homo sapiens 25-28 30936596-3 2019 The AMP-activated protein kinase (AMPK), as a metabolic sensor, could be activated with metformin and it can also launch a p53-dependent metabolic checkpoint and might inhibit cancer cell growth. Metformin 88-97 tumor protein p53 Homo sapiens 123-126 30936596-8 2019 Real-time PCR revealed that metformin induced apoptosis in TE8 and TE11 cells by activating p53, down-regulating Bcl-2 expression. Metformin 28-37 tumor protein p53 Homo sapiens 92-95 30936596-10 2019 Conclusion: Metformin induced apoptosis in ESCC by down-regulating Bcl-2 expression, and up-regulating p53 and induced apoptosis increased by 2-deoxy-d-glucose. Metformin 12-21 tumor protein p53 Homo sapiens 103-106 30442142-0 2018 Metformin causes cancer cell death through downregulation of p53-dependent differentiated embryo chondrocyte 1. Metformin 0-9 tumor protein p53 Homo sapiens 61-64 30442142-5 2018 We later clarified the effect of metformin on p53 protein stability using transient transfection and cycloheximide chase analyses. Metformin 33-42 tumor protein p53 Homo sapiens 46-49 30442142-6 2018 RESULTS: We observed that metformin represses cell cycle progression, thereby inducing subG1 populations, and had induced apoptosis through downregulation of p53 protein and a target gene, differentiated embryo chondrocyte 1 (DEC1). Metformin 26-35 tumor protein p53 Homo sapiens 158-161 30442142-9 2018 Examination of the mechanisms underlying metformin-induced HeLa cell death revealed that reduced stability of p53 in metformin-treated cells leads to decreases in DEC1 and induction of apoptosis. Metformin 41-50 tumor protein p53 Homo sapiens 110-113 30442142-9 2018 Examination of the mechanisms underlying metformin-induced HeLa cell death revealed that reduced stability of p53 in metformin-treated cells leads to decreases in DEC1 and induction of apoptosis. Metformin 117-126 tumor protein p53 Homo sapiens 110-113 30442142-10 2018 CONCLUSION: The involvement of DEC1 provides new insight into the positive or negative functional roles of p53 in the metformin-induced cytotoxicity in tumor cells. Metformin 118-127 tumor protein p53 Homo sapiens 107-110 30098371-10 2018 Although the increase in DNA pol beta was not significant, XRCC1 and p53 levels were significantly upregulated with metformin treatment in type 2 diabetes patients. Metformin 116-125 tumor protein p53 Homo sapiens 69-72 29334602-7 2018 The combination of TMZ and metformin enhanced AMPK phosphorylation and inhibited mammalian target of rapamycin phosphorylation, AKT phosphorylation, and p53 expression. Metformin 27-36 tumor protein p53 Homo sapiens 153-156 29185360-0 2018 Role of metformin on base excision repair pathway in p53 wild-type H2009 and HepG2 cancer cells. Metformin 8-17 tumor protein p53 Homo sapiens 53-56 29185360-3 2018 The understanding of the participation of oxidative stress in the action mechanism of metformin and its related effects on p53 and on DNA base excision repair (BER) system can help us to get closer to solve metformin puzzle in cancer. Metformin 86-95 tumor protein p53 Homo sapiens 123-126 29286156-0 2018 Metformin-induced activation of AMPK inhibits the proliferation and migration of human aortic smooth muscle cells through upregulation of p53 and IFI16. Metformin 0-9 tumor protein p53 Homo sapiens 138-141 29660403-10 2018 In contrast, both metformin and fulvene-5, inhibitors of NOX4, facilitated the reversal of TP53 WT and Mut adaptive responses from pro-survival to radio-sensitization and vice versa, respectively. Metformin 18-27 tumor protein p53 Homo sapiens 91-95 29660403-13 2018 Under these conditions NOX4 expression was inhibited by about 50%, resulting in a reversal in the expression of the TP53 WT and Mut survivin-associated adaptive responses as was observed following metformin and fulvene-5 treatment. Metformin 197-206 tumor protein p53 Homo sapiens 116-120 29286156-8 2018 In addition, metformin was able to activate p53, IFI16 and AMPK, in order to inhibit proliferation and migration of HASMCs. Metformin 13-22 tumor protein p53 Homo sapiens 44-47 29286156-9 2018 Furthermore, siRNA-mediated knockdown of p53 and IFI16 attenuated AMPK activation and reversed the suppressive effects of metformin. Metformin 122-131 tumor protein p53 Homo sapiens 41-44 29286156-11 2018 These results indicated that metformin-induced activation of AMPK suppresses the proliferation and migration of HASMCs by upregulating p53 and IFI16. Metformin 29-38 tumor protein p53 Homo sapiens 135-138 28802253-0 2017 The Combination of Metformin and Valproic Acid Induces Synergistic Apoptosis in the Presence of p53 and Androgen Signaling in Prostate Cancer. Metformin 19-28 tumor protein p53 Homo sapiens 96-99 29285650-10 2018 Furthermore, gemigliptin augments the inhibitory effect of metformin on proliferation and migration through involvement of matrix metalloproteinase-2, matrix metalloproteinase-9, p53, p21, VCAM-1, and ERK in thyroid carcinoma cells. Metformin 59-68 tumor protein p53 Homo sapiens 179-182 31508193-6 2018 The presence of the R337H TP53 mutation suggests a mechanism for the observed response to metformin. Metformin 90-99 tumor protein p53 Homo sapiens 26-30 29423021-0 2018 Association of p53 and mitochondrial gene with chemosensitization by metformin in ovarian cancer. Metformin 69-78 tumor protein p53 Homo sapiens 15-18 29423021-1 2018 Objective: This study aims to investigate the association of p53 and D-loop gene with drug resistance and sensitization induced by metformin in ovarian cancer. Metformin 131-140 tumor protein p53 Homo sapiens 61-64 29167573-3 2017 We studied the anti-cancer activity of metformin on colorectal cancer (CRC) by using the drug to treat HT29, HCT116 and HCT116 p53-/- CRC cells. Metformin 39-48 tumor protein p53 Homo sapiens 127-130 28967197-7 2017 Furthermore, inactivation of mitochondria and activation of p53 protein are observed during MGNP treatment, which provides evidence for metformin-induced cell apoptosis pathways. Metformin 136-145 tumor protein p53 Homo sapiens 60-63 28618116-1 2017 Mutations in the tumor suppressor p53 are highly prevalent in cancers and are known to influence the sensitivity of cells to various chemotherapeutics including the anti-cancer candidates 1,25-dihydrovitamin D3 [1,25D3] and metformin. Metformin 224-233 tumor protein p53 Homo sapiens 34-37 27128966-4 2017 Metformin promoted cytotoxic effects only in the cancer cells irrespective of the p53 status and not in the normal primary-cultured cells. Metformin 0-9 tumor protein p53 Homo sapiens 82-85 29085821-7 2017 Additionally, metformin increased the expression levels of p53, Bax, Bad while it reduced expression levels of Akt, Bcl-2, and Mdm2. Metformin 14-23 tumor protein p53 Homo sapiens 59-62 28193839-3 2017 In this study, we report that, under glucose deprivation, metformin inhibited expression of DeltaNp63alpha, a p53 family member involved in cell adhesion pathways, resulting in disruption of cell matrix adhesion and subsequent apoptosis in human squamous carcinoma cells. Metformin 58-67 tumor protein p53 Homo sapiens 110-113 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 tumor protein p53 Homo sapiens 139-142 28052008-0 2017 Targeting P-glycoprotein function, p53 and energy metabolism: Combination of metformin and 2-deoxyglucose reverses the multidrug resistance of MCF-7/Dox cells to doxorubicin. Metformin 77-86 tumor protein p53 Homo sapiens 35-38 27919208-10 2017 Metformin reduces tumour cell growth and metastasis by activating the p53 tumour suppressor gene. Metformin 0-9 tumor protein p53 Homo sapiens 70-73 28052008-8 2017 Taken together, combination of metformin and 2-deoxyglucose reverses MDR of MCF-7/Dox cells by recovering p53 function and increasing doxorubicin accumulation. Metformin 31-40 tumor protein p53 Homo sapiens 106-109 27109601-5 2016 We found that metformin inhibited UVC-induced upregulation of p53, as well as downregulated the expression of two DNA damage markers: gammaH2AX and p-chk2. Metformin 14-23 tumor protein p53 Homo sapiens 62-65 27274280-0 2016 Metformin induces apoptosis of human hepatocellular carcinoma HepG2 cells by activating an AMPK/p53/miR-23a/FOXA1 pathway. Metformin 0-9 tumor protein p53 Homo sapiens 96-99 27109601-9 2016 However, resveratrol displayed synergism when combined with metformin as shown by the downregulation of p53/gammaH2AX/p-chk2. Metformin 60-69 tumor protein p53 Homo sapiens 104-107 27274280-5 2016 Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin. Metformin 115-124 tumor protein p53 Homo sapiens 91-94 27274280-5 2016 Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin. Metformin 200-209 tumor protein p53 Homo sapiens 91-94 27274280-5 2016 Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin. Metformin 200-209 tumor protein p53 Homo sapiens 158-161 27274280-5 2016 Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin. Metformin 115-124 tumor protein p53 Homo sapiens 158-161 27274280-5 2016 Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin. Metformin 200-209 tumor protein p53 Homo sapiens 158-161 27274280-6 2016 In summary, we unraveled a novel AMPK/p53/miR-23a/FOXA1 axis in the regulation of apoptosis in HCC, and the application of metformin could, therefore, be effective in the treatment of HCC. Metformin 123-132 tumor protein p53 Homo sapiens 38-41 27274280-5 2016 Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin. Metformin 115-124 tumor protein p53 Homo sapiens 158-161 27274280-5 2016 Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin. Metformin 200-209 tumor protein p53 Homo sapiens 91-94 27274280-5 2016 Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin. Metformin 200-209 tumor protein p53 Homo sapiens 158-161 27274280-5 2016 Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin. Metformin 200-209 tumor protein p53 Homo sapiens 158-161 26956973-3 2016 p53 wild-type and p53 mutant breast cancer cells were treated with metformin, and expression of TTP and c-Myc was analyzed by semi-quantitative RT-PCR, Western blots, and promoter activity assay. Metformin 67-76 tumor protein p53 Homo sapiens 0-3 26956973-5 2016 Metformin induces the expression of tristetraprolin (TTP) in breast cancer cells in a p53-independent manner. Metformin 0-9 tumor protein p53 Homo sapiens 86-89 26629991-0 2015 Metformin and Resveratrol Inhibited High Glucose-Induced Metabolic Memory of Endothelial Senescence through SIRT1/p300/p53/p21 Pathway. Metformin 0-9 tumor protein p53 Homo sapiens 119-122 26900800-5 2016 We found that both Tennovin-1 and BI2536 increased the anti-neoplastic activity of metformin, an inhibitor of oxidative phosphorylation, in a p53 dependent manner. Metformin 83-92 tumor protein p53 Homo sapiens 142-145 26677765-5 2015 Specifically, we show that metformin enhances adult NPC proliferation and self-renewal dependent upon the p53 family member and transcription factor TAp73, while it promotes neuronal differentiation of these cells by activating the AMPK-aPKC-CBP pathway. Metformin 27-36 tumor protein p53 Homo sapiens 106-109 26885449-5 2015 In association with the reduction of MYC onco-protein, metformin significantly restored p53 tumor suppressor gene expression. Metformin 55-64 tumor protein p53 Homo sapiens 88-91 26599019-0 2015 Metformin Radiosensitizes p53-Deficient Colorectal Cancer Cells through Induction of G2/M Arrest and Inhibition of DNA Repair Proteins. Metformin 0-9 tumor protein p53 Homo sapiens 26-29 26599019-1 2015 The present study addressed whether the combination of metformin and ionizing radiation (IR) would show enhanced antitumor effects in radioresistant p53-deficient colorectal cancer cells, focusing on repair pathways for IR-induced DNA damage. Metformin 55-64 tumor protein p53 Homo sapiens 149-152 26599019-2 2015 Metformin caused a higher reduction in clonogenic survival as well as greater radiosensitization and inhibition of tumor growth of p53-/- than of p53+/+ colorectal cancer cells and xenografts. Metformin 0-9 tumor protein p53 Homo sapiens 131-134 26599019-2 2015 Metformin caused a higher reduction in clonogenic survival as well as greater radiosensitization and inhibition of tumor growth of p53-/- than of p53+/+ colorectal cancer cells and xenografts. Metformin 0-9 tumor protein p53 Homo sapiens 146-149 26599019-5 2015 In conclusion, metformin enhanced radiosensitivity by inducing G2/M arrest and reducing the expression of DNA repair proteins even in radioresistant HCT116 p53-/- colorectal cancer cells and tumors. Metformin 15-24 tumor protein p53 Homo sapiens 156-159 26885449-6 2015 The distinctive effects of metformin and PP242 on MYC reduction and P53 restoration suggested that metformin inhibited cell growth through a different pathway from PP242 in salivary carcinoma cells. Metformin 99-108 tumor protein p53 Homo sapiens 68-71 26225749-5 2015 Treatment of MCF-7 cells with metformin or phenformin induced increase in p53 protein levels and the transcription of its downstream target genes, Bax and p21, in a dose-dependent manner. Metformin 30-39 tumor protein p53 Homo sapiens 74-77 26383681-7 2015 Interestingly, metformin may enhance radiation response specifically in certain genetic backgrounds, such as in cells with loss of the tumor suppressors p53 and LKB1, giving rise to a therapeutic ratio and potential predictive biomarkers. Metformin 15-24 tumor protein p53 Homo sapiens 153-156 26225749-0 2015 p53 is required for metformin-induced growth inhibition, senescence and apoptosis in breast cancer cells. Metformin 20-29 tumor protein p53 Homo sapiens 0-3 26225749-2 2015 The tumor inhibitory effect of metformin on p53-mutated breast cancer cells remains unclear. Metformin 31-40 tumor protein p53 Homo sapiens 44-47 26225749-6 2015 Moreover, we demonstrated that AMPK-mTOR signaling played a role in metformin-induced p53 up-regulation. Metformin 68-77 tumor protein p53 Homo sapiens 86-89 26225749-3 2015 Data from the present study demonstrated that p53 knockdown or mutation has a negative effect on metformin or phenformin-induced growth inhibition, senescence and apoptosis in breast cancer cells. Metformin 97-106 tumor protein p53 Homo sapiens 46-49 26225749-4 2015 We also found that p53 reactivating agent nutlin-3alpha and CP/31398 promoted metformin-induced growth inhibition, senescence and apoptosis in MCF-7 (wt p53) and MDA-MB-231 (mt p53) cells, respectively. Metformin 78-87 tumor protein p53 Homo sapiens 19-22 26225749-7 2015 The present study showed that p53 is required for metformin or phenformin-induced growth inhibition, senescence and apoptosis in breast cancer cells. Metformin 50-59 tumor protein p53 Homo sapiens 30-33 26225749-4 2015 We also found that p53 reactivating agent nutlin-3alpha and CP/31398 promoted metformin-induced growth inhibition, senescence and apoptosis in MCF-7 (wt p53) and MDA-MB-231 (mt p53) cells, respectively. Metformin 78-87 tumor protein p53 Homo sapiens 153-156 26225749-4 2015 We also found that p53 reactivating agent nutlin-3alpha and CP/31398 promoted metformin-induced growth inhibition, senescence and apoptosis in MCF-7 (wt p53) and MDA-MB-231 (mt p53) cells, respectively. Metformin 78-87 tumor protein p53 Homo sapiens 153-156 26225749-8 2015 The combination of metformin with p53 reactivating agents, like nutlin-3alpha and CP/31398, is a promising strategy for improving metformin-mediated anti-cancer therapy, especially for tumors with p53 mutations. Metformin 19-28 tumor protein p53 Homo sapiens 197-200 26225749-8 2015 The combination of metformin with p53 reactivating agents, like nutlin-3alpha and CP/31398, is a promising strategy for improving metformin-mediated anti-cancer therapy, especially for tumors with p53 mutations. Metformin 130-139 tumor protein p53 Homo sapiens 34-37 26225749-8 2015 The combination of metformin with p53 reactivating agents, like nutlin-3alpha and CP/31398, is a promising strategy for improving metformin-mediated anti-cancer therapy, especially for tumors with p53 mutations. Metformin 130-139 tumor protein p53 Homo sapiens 197-200 26196392-7 2015 Most importantly, the up-regulation of AMPK, p53, p21CIP1, p27KIP1 and the down-regulation of cyclinD1 are involved in the anti-tumor action of metformin in vivo. Metformin 144-153 tumor protein p53 Homo sapiens 45-48 26196392-9 2015 AMPK, p53, p21CIP1, p27KIP1 and cyclinD1 are involved in the inhibition of tumor growth that is induced by metformin and cell cycle arrest in ESCC. Metformin 107-116 tumor protein p53 Homo sapiens 6-9 25505174-3 2015 Furthermore, we also provide evidence that Plk1 inhibition makes PCa cells carrying WT p53 much more sensitive to low-dose metformin treatment. Metformin 123-132 tumor protein p53 Homo sapiens 87-90 25955843-8 2015 While recent studies showed that treatment with only TRAIL was not effective against pancreatic cancer cells, the present data showed that metformin sensitized p53-mutated pancreatic cancer cells to TRAIL. Metformin 139-148 tumor protein p53 Homo sapiens 160-163 25495168-1 2015 The aim of this proof-of-concept study was to determine the effects of three-month Metformin therapy on the expression of tumor-regulatory genes (p53, cyclin D2 and BCL-2) in the endometrium of women with polycystic ovary syndrome (PCOS). Metformin 83-92 tumor protein p53 Homo sapiens 146-149 25495168-8 2015 Tumor suppressor gene (p53) was significantly up-regulated after Metformin (10 out of 14 women), with p value 0.016. Metformin 65-74 tumor protein p53 Homo sapiens 23-26 25495168-10 2015 In conclusion, Metformin therapy improved clinical and metabolic parameters in women with PCOS and up-regulated p53 tumor suppressor gene significantly. Metformin 15-24 tumor protein p53 Homo sapiens 112-115 25505174-4 2015 Mechanistically, we found that co-treatment with BI2536 and metformin induced p53-dependent apoptosis and further activated the p53/Redd-1 pathway. Metformin 60-69 tumor protein p53 Homo sapiens 78-81 25505174-4 2015 Mechanistically, we found that co-treatment with BI2536 and metformin induced p53-dependent apoptosis and further activated the p53/Redd-1 pathway. Metformin 60-69 tumor protein p53 Homo sapiens 128-131 24970682-11 2014 Furthermore, upregulation of death receptor 5 by metformin-mediated Sirt1 downregulation enhanced the sensitivity of wild-type p53 cancer cells to TRAIL-induced apoptosis. Metformin 49-58 tumor protein p53 Homo sapiens 127-130 25131770-11 2015 Metformin, an AMPK activator, more strongly suppressed cell growth in p53-mutant cell lines with inactive SIRT1 than in p53-mutant cell lines with active SIRT1. Metformin 0-9 tumor protein p53 Homo sapiens 70-73 25131770-11 2015 Metformin, an AMPK activator, more strongly suppressed cell growth in p53-mutant cell lines with inactive SIRT1 than in p53-mutant cell lines with active SIRT1. Metformin 0-9 tumor protein p53 Homo sapiens 120-123 25131770-13 2015 Metformin could be a therapeutic drug for HCC in patients with mutated p53, inactivated SIRT1, and AMPK expression. Metformin 0-9 tumor protein p53 Homo sapiens 71-74 24970682-0 2014 Metformin induces microRNA-34a to downregulate the Sirt1/Pgc-1alpha/Nrf2 pathway, leading to increased susceptibility of wild-type p53 cancer cells to oxidative stress and therapeutic agents. Metformin 0-9 tumor protein p53 Homo sapiens 131-134 24970682-4 2014 Using human cancer cell lines that exhibit differential expression of p53, we found that metformin reduced Sirt1 protein levels in cancer cells bearing wild-type p53, but did not affect Sirt1 protein levels in cancer cell lines harboring mutant forms of p53. Metformin 89-98 tumor protein p53 Homo sapiens 70-73 24970682-4 2014 Using human cancer cell lines that exhibit differential expression of p53, we found that metformin reduced Sirt1 protein levels in cancer cells bearing wild-type p53, but did not affect Sirt1 protein levels in cancer cell lines harboring mutant forms of p53. Metformin 89-98 tumor protein p53 Homo sapiens 162-165 24970682-4 2014 Using human cancer cell lines that exhibit differential expression of p53, we found that metformin reduced Sirt1 protein levels in cancer cells bearing wild-type p53, but did not affect Sirt1 protein levels in cancer cell lines harboring mutant forms of p53. Metformin 89-98 tumor protein p53 Homo sapiens 162-165 24970682-5 2014 Metformin-induced p53 protein levels in wild-type p53 cancer cells resulted in upregulation of microRNA (miR)-34a. Metformin 0-9 tumor protein p53 Homo sapiens 18-21 24970682-5 2014 Metformin-induced p53 protein levels in wild-type p53 cancer cells resulted in upregulation of microRNA (miR)-34a. Metformin 0-9 tumor protein p53 Homo sapiens 50-53 24970682-12 2014 Our results demonstrated that metformin induces miR-34a to suppress the Sirt1/Pgc-1alpha/Nrf2 pathway and increases susceptibility of wild-type p53 cancer cells to oxidative stress and TRAIL-induced apoptosis. Metformin 30-39 tumor protein p53 Homo sapiens 144-147 24504677-3 2014 The biomolecular characteristics of tumors, such as appropriate expression of organic cation transporters or genetic alterations including p53, K-ras, LKB1, and PI3K may impact metformin"s anticancer efficiency. Metformin 177-186 tumor protein p53 Homo sapiens 139-142 23999197-8 2014 Accordingly, the improvement of insulin sensitivity with surgery-induced weight loss (+51%, P=0.01) and metformin (+42%, P=0.02) led to increased adipose p53. Metformin 104-113 tumor protein p53 Homo sapiens 154-157 23982736-0 2013 Low concentration of metformin induces a p53-dependent senescence in hepatoma cells via activation of the AMPK pathway. Metformin 21-30 tumor protein p53 Homo sapiens 41-44 24190973-8 2014 The activation of p53 through AMPK-mediated MDMX phosphorylation and inactivation was further confirmed by using cell and animal model systems with two AMPK activators, metformin and salicylate (the active form of aspirin). Metformin 169-178 tumor protein p53 Homo sapiens 18-21 23982736-8 2013 In addition, p53 siRNA transfection attenuated metformin-induced SA-beta-gal staining. Metformin 47-56 tumor protein p53 Homo sapiens 13-16 23982736-9 2013 Intriguingly, co-expression of SIRT1 and p53 dramatically reduced the levels of Ac-p53, however, low doses of metformin treatment partially reversed the effect of SIRT1 on p53 acetylation and elevated SA-beta-gal activity. Metformin 110-119 tumor protein p53 Homo sapiens 83-86 23982736-9 2013 Intriguingly, co-expression of SIRT1 and p53 dramatically reduced the levels of Ac-p53, however, low doses of metformin treatment partially reversed the effect of SIRT1 on p53 acetylation and elevated SA-beta-gal activity. Metformin 110-119 tumor protein p53 Homo sapiens 83-86 23982736-10 2013 These observations indicate that activation of the AMPK pathway promotes senescence in hepatoma cells exposed to low concentrations of metformin in a p53-dependent manner. Metformin 135-144 tumor protein p53 Homo sapiens 150-153 23891087-0 2013 Contributions of AMPK and p53 dependent signaling to radiation response in the presence of metformin. Metformin 91-100 tumor protein p53 Homo sapiens 26-29 23891087-2 2013 Metformin activates AMPK that in turn can launch a p53-dependent metabolic checkpoint. Metformin 0-9 tumor protein p53 Homo sapiens 51-54 23891087-8 2013 Loss of AMPK sensitized cells to the anti-proliferative effects of metformin, while loss of p53 promoted both the growth inhibitory and toxic effects of metformin. Metformin 153-162 tumor protein p53 Homo sapiens 92-95 23891087-4 2013 Since radiation-induced signaling also involves AMPK and p53, we investigated their importance in mediating responses to metformin and radiation. Metformin 121-130 tumor protein p53 Homo sapiens 57-60 23891087-10 2013 CONCLUSIONS: The anti-proliferative activity of metformin may confer benefit in combination with radiotherapy, and this benefit is intensified upon loss of AMPK or p53 signaling. Metformin 48-57 tumor protein p53 Homo sapiens 164-167 23303309-3 2013 Also key to better understanding is why and how the anti-diabetic drug metformin (the world"s most prescribed pharmaceutical product) preferentially kills oxidant-deficient mesenchymal p53(- -) cells. Metformin 71-80 tumor protein p53 Homo sapiens 185-188 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 tumor protein p53 Homo sapiens 69-72 23620761-0 2013 Metformin downregulates the insulin/IGF-I signaling pathway and inhibits different uterine serous carcinoma (USC) cells proliferation and migration in p53-dependent or -independent manners. Metformin 0-9 tumor protein p53 Homo sapiens 151-154 23620761-8 2013 Our results show that metformin interacts with the IGF pathway, and induces apoptosis and inhibition of proliferation and migration of USC cell lines with both wild type and mutant p53. Metformin 22-31 tumor protein p53 Homo sapiens 181-184 22773548-9 2013 Cell line studies showed that metformin inhibits hepatocyte proliferation and induces cell cycle arrest at G0/G1 phase via AMP-activated protein kinase and its upstream kinase LKB1 to upregulate p21/Cip1 and p27/Kip1 and downregulate cyclin D1 in a dose-dependent manner, but independent of p53. Metformin 30-39 tumor protein p53 Homo sapiens 291-294 22378745-0 2012 A novel inverse relationship between metformin-triggered AMPK-SIRT1 signaling and p53 protein abundance in high glucose-exposed HepG2 cells. Metformin 37-46 tumor protein p53 Homo sapiens 82-85 24335168-6 2013 In addition, we found USP7, a positive regulator of tumor suppressor p53, as a new molecular target of metformin. Metformin 103-112 tumor protein p53 Homo sapiens 69-72 22378745-5 2012 Metformin induced activation of AMPK and SIRT1 and decreased p53 protein abundance. Metformin 0-9 tumor protein p53 Homo sapiens 61-64 22378745-8 2012 In addition, overexpression of p53 decreased SIRT1 gene expression and protein abundance, as well as AMPK activity in metformin-treated cells. Metformin 118-127 tumor protein p53 Homo sapiens 31-34 22090360-6 2012 The effect of the drug metformin on overcoming mutant p53-associated radiation resistance was examined in vitro as well as in vivo, using an orthotopic xenograft model. Metformin 23-32 tumor protein p53 Homo sapiens 54-57 22442140-1 2012 Focus on "A novel inverse relationship between metformin-triggered AMPK-SIRT1 signaling and p53 protein abundance in high glucose-exposed HepG2 cells". Metformin 47-56 tumor protein p53 Homo sapiens 92-95 22090360-10 2012 The mitochondrial agent metformin potentiated the effects of radiation in the presence of a disruptive TP53 mutation partially via senescence. Metformin 24-33 tumor protein p53 Homo sapiens 103-107 22090360-13 2012 Metformin can serve as a radiosensitizer for HNSCC with disruptive TP53, presaging the possibility of personalizing HNSCC treatment. Metformin 0-9 tumor protein p53 Homo sapiens 67-71 20215500-0 2010 Targeting cancer cell metabolism: the combination of metformin and 2-deoxyglucose induces p53-dependent apoptosis in prostate cancer cells. Metformin 53-62 tumor protein p53 Homo sapiens 90-93 21776823-5 2011 Metformin induced apoptosis by arresting cells in G1 phase and reducing cyclin D level and increasing the expression of p21 and cyclin E. Molecular and cellular studies indicated that metformin significantly elevated p53 and Bax levels and reduced STAT3 and Bcl-2. Metformin 0-9 tumor protein p53 Homo sapiens 217-220 21776823-5 2011 Metformin induced apoptosis by arresting cells in G1 phase and reducing cyclin D level and increasing the expression of p21 and cyclin E. Molecular and cellular studies indicated that metformin significantly elevated p53 and Bax levels and reduced STAT3 and Bcl-2. Metformin 184-193 tumor protein p53 Homo sapiens 217-220 21655990-11 2011 Messenger RNA expression was significantly downregulated by metformin for PDE3B (phosphodiesterase 3B, cGMP-inhibited; a critical regulator of cAMP levels that affect activation of AMP-activated protein kinase, AMPK), confirmed by immunohistochemistry, SSR3, TP53 and CCDC14. Metformin 60-69 tumor protein p53 Homo sapiens 259-263 21655990-13 2011 Gene set analysis additionally revealed that p53, BRCA1 and cell cycle pathways also had reduced expression following metformin. Metformin 118-127 tumor protein p53 Homo sapiens 45-48 21540236-5 2011 We show that metformin increases REDD1 expression in a p53-dependent manner. Metformin 13-22 tumor protein p53 Homo sapiens 55-58 21540236-8 2011 Finally, we show the contribution of p53 in mediating metformin action in prostate cancer cells. Metformin 54-63 tumor protein p53 Homo sapiens 37-40 21540236-9 2011 These results highlight the p53/REDD1 axis as a new molecular target in anticancer therapy in response to metformin treatment. Metformin 106-115 tumor protein p53 Homo sapiens 28-31 21776823-8 2011 Furthermore, MEK inhibitor significantly suppressed metformin-induced p53 and Bax elevation while ERK inhibitor generated a slight reduction in p53 levels. Metformin 52-61 tumor protein p53 Homo sapiens 70-73 21776823-11 2011 All these results suggested that metformin activated p53, Bax, and induced tumor cell apoptosis through the ERK signaling pathway. Metformin 33-42 tumor protein p53 Homo sapiens 53-56 20215500-6 2010 At the cellular level, the combination of metformin and 2DG induced p53-dependent apoptosis via the energy sensor pathway AMP kinase, and the reexpression of a functional p53 in p53-deficient prostate cancer cells restored caspase-3 activity. Metformin 42-51 tumor protein p53 Homo sapiens 68-71 20215500-6 2010 At the cellular level, the combination of metformin and 2DG induced p53-dependent apoptosis via the energy sensor pathway AMP kinase, and the reexpression of a functional p53 in p53-deficient prostate cancer cells restored caspase-3 activity. Metformin 42-51 tumor protein p53 Homo sapiens 171-174 20215500-7 2010 In addition to apoptosis, the combination of metformin and 2DG arrested prostate cancer cells in G(2)-M. This G(2)-M arrest was independent of p53 and correlated with a stronger decrease in cell viability than obtained with either drug. Metformin 45-54 tumor protein p53 Homo sapiens 143-146 34676202-11 2021 In metformin-treated samples, the CEBPA, TP53 and USF1 transcription factors appeared to be involved in the regulation of several factors (SOD1, SOD2, CAT, GLRX, GSTP1) blocking ROS. Metformin 3-12 tumor protein p53 Homo sapiens 41-45 17638885-0 2007 Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth. Metformin 46-55 tumor protein p53 Homo sapiens 76-79 17638885-2 2007 Treatment with metformin selectively suppressed the tumor growth of HCT116 p53(-/-) xenografts. Metformin 15-24 tumor protein p53 Homo sapiens 75-78 17638885-3 2007 Following treatment with metformin, we detected increased apoptosis in p53(-/-) tumor sections and an enhanced susceptibility of p53(-/-) cells to undergo apoptosis in vitro when subject to nutrient deprivation. Metformin 25-34 tumor protein p53 Homo sapiens 71-74 17638885-3 2007 Following treatment with metformin, we detected increased apoptosis in p53(-/-) tumor sections and an enhanced susceptibility of p53(-/-) cells to undergo apoptosis in vitro when subject to nutrient deprivation. Metformin 25-34 tumor protein p53 Homo sapiens 129-132 17638885-8 2007 Treatment with either metformin or AICAR also led to enhanced fatty acid beta-oxidation in p53(+/+) MEFs, but not in p53(-/-) MEFs. Metformin 22-31 tumor protein p53 Homo sapiens 91-94 17638885-10 2007 Metformin-treated cells compensated for this suppression of oxidative phosphorylation by increasing their rate of glycolysis in a p53-dependent manner. Metformin 0-9 tumor protein p53 Homo sapiens 130-133 17638885-11 2007 Together, these data suggest that metformin treatment forces a metabolic conversion that p53(-/-) cells are unable to execute. Metformin 34-43 tumor protein p53 Homo sapiens 89-92 17638885-12 2007 Thus, metformin is selectively toxic to p53-deficient cells and provides a potential mechanism for the reduced incidence of tumors observed in patients being treated with metformin. Metformin 6-15 tumor protein p53 Homo sapiens 40-43 17638885-12 2007 Thus, metformin is selectively toxic to p53-deficient cells and provides a potential mechanism for the reduced incidence of tumors observed in patients being treated with metformin. Metformin 171-180 tumor protein p53 Homo sapiens 40-43 33236135-0 2021 Metformin induces apoptosis and inhibits migration by activating the AMPK/p53 axis and suppressing PI3K/AKT signaling in human cervical cancer cells. Metformin 0-9 tumor protein p53 Homo sapiens 74-77 33236135-5 2021 Following metformin treatment, the protein expression levels of p-AMP-activated protein kinase (p-AMPK), which promotes cell death, and the tumor suppressor protein p-p53 were remarkably upregulated in CaSki and C33A cells compared with the control group. Metformin 10-19 tumor protein p53 Homo sapiens 167-170 34528900-8 2021 Treatment with a sub-lethal dose of cisplatin increased Jarid1b expression, yet downregulated P53 levels, protecting A549Res cells from metformin-induced chemosensitization to cisplatin and favored a glycolytic phenotype. Metformin 136-145 tumor protein p53 Homo sapiens 94-97 34638899-9 2021 The present results indicate a shift towards synergism in cells with mutant or null p53, treated with olaparib combined with metformin, providing a new approach to the treatment of gynecologic cancers. Metformin 125-134 tumor protein p53 Homo sapiens 84-87 34528900-0 2021 Metformin-induced chemosensitization to cisplatin depends on P53 status and is inhibited by Jarid1b overexpression in non-small cell lung cancer cells. Metformin 0-9 tumor protein p53 Homo sapiens 61-64 34528900-3 2021 Here we test if the presence of P53 could predict the activity of metformin as an adjuvant for cisplatin-based therapy in non-small cell lung cancer (NSCLC). Metformin 66-75 tumor protein p53 Homo sapiens 32-35 34528900-7 2021 Metformin sensitized A549 and HCC 827 cells (but not H1299 and H358 cells) to cisplatin in a P53-dependent manner, changing its subcellular localization to the mitochondria. Metformin 0-9 tumor protein p53 Homo sapiens 93-96 34528900-10 2021 In conclusion, metformin could potentially be used as an adjuvant for cisplatin-based therapy in NSCLC cells if wild type P53 is present. Metformin 15-24 tumor protein p53 Homo sapiens 122-125 34135572-0 2021 Metformin Decreases Insulin Resistance in Type 1 Diabetes Through Regulating P53 and RAP2A in vitro and in vivo (Retraction). Metformin 0-9 tumor protein p53 Homo sapiens 77-80 34564972-3 2021 We evaluated the antitumoral effect of iRNA-PFK-1 and the combined therapy iRNA-PFK-1 + metformin in RKO p53-positive cells. Metformin 88-97 tumor protein p53 Homo sapiens 105-108 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 tumor protein p53 Homo sapiens 1192-1196 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 tumor protein p53 Homo sapiens 1197-1202 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 tumor protein p53 Homo sapiens 1203-1206