PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 27517917-10 2016 Metformin treatment reduced breast cancer cell viability, increased miR-26a expression, and led to a reduction in BCL-2, EZH2, and PTEN expression. Metformin 0-9 BCL2 apoptosis regulator Homo sapiens 114-119 28927780-9 2017 The combination of specific inhibitors of ERK1/2, JNK or PI3K/Akt pathway and metformin further promoted cell apoptosis and the up-regulation of p21, Bax, Bad, cleaved caspase-3 and -9 as well as the down-regulation of Bcl-2 mediated by metformin alone, but inhibition of p38 pathway exhibited the opposite results. Metformin 78-87 BCL2 apoptosis regulator Homo sapiens 219-224 28345832-9 2017 Furthermore, metformin exposure resultedin decreased STAT3 activation and down-regulation of anti-apoptotic protein Bcl-2 and Mcl-1 expression. Metformin 13-22 BCL2 apoptosis regulator Homo sapiens 116-121 28378944-9 2017 We found that metformin can exert growth-suppressive effects on these cell lines via inhibition of p-Akt activity and the Bcl-2 family. Metformin 14-23 BCL2 apoptosis regulator Homo sapiens 122-127 27246734-8 2016 Moreover, Western blot and immunofluorescence results indicated that caspase 3 activation was reduced, whereas bcl-2 level was significantly increased by metformin. Metformin 154-163 BCL2 apoptosis regulator Homo sapiens 111-116 27168791-8 2016 Moreover, metformin downregulated the expression of the anti-apoptotic proteins B-cell lymphoma 2 (BCL-2) and myeloid cell leukemia-1, and upregulated the expression of the pro-apoptotic BCL-2-associated X protein in MDA-MB-231 cells. Metformin 10-19 BCL2 apoptosis regulator Homo sapiens 80-97 27391065-4 2016 Metformin also triggers the apoptotic pathway, shown by the decreased expression of Bcl-2 and HSP27, HSP60 and HSP70, and enhanced membrane exposure of annexin V, resulting in activation of caspase-3 apoptotic effector. Metformin 0-9 BCL2 apoptosis regulator Homo sapiens 84-89 27168791-8 2016 Moreover, metformin downregulated the expression of the anti-apoptotic proteins B-cell lymphoma 2 (BCL-2) and myeloid cell leukemia-1, and upregulated the expression of the pro-apoptotic BCL-2-associated X protein in MDA-MB-231 cells. Metformin 10-19 BCL2 apoptosis regulator Homo sapiens 99-104 27168791-8 2016 Moreover, metformin downregulated the expression of the anti-apoptotic proteins B-cell lymphoma 2 (BCL-2) and myeloid cell leukemia-1, and upregulated the expression of the pro-apoptotic BCL-2-associated X protein in MDA-MB-231 cells. Metformin 10-19 BCL2 apoptosis regulator Homo sapiens 187-192 26266765-9 2015 Metformin induced apoptosis by down-regulating Bcl-2 and Bcl-xL expression, and up-regulating Bax and Cytochrome c expression. Metformin 0-9 BCL2 apoptosis regulator Homo sapiens 47-52 26111693-6 2015 The expressions of caspase-3 and Bax protein were significantly increased (P<0.05) and Bcl-2 protein expression was decreased (P<0.05) with a lowered Bcl-2/Bax ratio in AGEs-treated fibroblasts (P<0.05), and such changes were significantly reversed by metformin treatment (P<0.05). Metformin 261-270 BCL2 apoptosis regulator Homo sapiens 156-161 26056043-10 2015 Taken together, the combination of metformin and aspirin significantly inhibited pancreatic cancer cell growth in vitro and in vivo by regulating the pro- and anti-apoptotic Bcl-2 family members, supporting the continued investigation of this two drug combination as chemopreventive or chemotherapeutic agents for pancreatic cancer. Metformin 35-44 BCL2 apoptosis regulator Homo sapiens 174-179 26056043-0 2015 Metformin combined with aspirin significantly inhibit pancreatic cancer cell growth in vitro and in vivo by suppressing anti-apoptotic proteins Mcl-1 and Bcl-2. Metformin 0-9 BCL2 apoptosis regulator Homo sapiens 154-159 26056043-7 2015 Remarkably, metformin combined with aspirin significantly downregulated the anti-apoptotic proteins Mcl-1 and Bcl-2, and upregulated the pro-apoptotic proteins Bim and Puma, as well as interrupted their interactions. Metformin 12-21 BCL2 apoptosis regulator Homo sapiens 110-115 26111693-7 2015 CONCLUSION: Metformin can antagonize AGEs-induced apoptosis in human dermal fibroblasts by regulating the expressions of caspase-3, Bax and Bcl-2. Metformin 12-21 BCL2 apoptosis regulator Homo sapiens 140-145 25492486-0 2015 Metformin sensitizes hepatocellular carcinoma to arsenic trioxide-induced apoptosis by downregulating Bcl2 expression. Metformin 0-9 BCL2 apoptosis regulator Homo sapiens 102-106 25595658-9 2015 Furthermore, co-treatment of hNSCs with metformin significantly blocked AGE-mediated reductions in the expression levels of several neuroprotective genes (PPARgamma, Bcl-2 and CREB). Metformin 40-49 BCL2 apoptosis regulator Homo sapiens 166-171 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 BCL2 apoptosis regulator Homo sapiens 165-170 25492486-4 2015 Metformin is reported to decrease Bcl2 expression, and the purpose of this study was to verify whether metformin could potentiate the anti-HCC efficacy of ATO in vitro. Metformin 0-9 BCL2 apoptosis regulator Homo sapiens 34-38 25492486-7 2015 Furthermore, this activity proceeded via a mechanism involving metformin-induced downregulation of Bcl2. Metformin 63-72 BCL2 apoptosis regulator Homo sapiens 99-103 25542900-9 2015 Ritonavir and metformin effectively suppressed AKT and mTORC1 phosphorylation and prosurvival BCL-2 family member MCL-1 expression in multiple myeloma cell lines in vitro and in vivo. Metformin 14-23 BCL2 apoptosis regulator Homo sapiens 94-99 26688757-3 2015 In metformin-sensitive cells, autophagy was not induced but rather it blocked proliferation by means of arresting cells in the S and G2/M phases which was associated with the downregulation of cyclin A, cyclin B1, and cdc2, but not that of cyclin E. In 10E1-CEM cells that overexpress Bcl-2 and are drug-resistant, the effect of metformin on proliferation was more pronounced, also inducing the activation of the caspases 3/7 and hence apoptosis. Metformin 3-12 BCL2 apoptosis regulator Homo sapiens 285-290 26514477-12 2015 CONCLUSIONS: Metformin was able to induce apoptosis in primary ovarian cancer cells by modulating the expression of Bcl-2 family proteins. Metformin 13-22 BCL2 apoptosis regulator Homo sapiens 116-121 25419360-6 2014 As a result, protein abundance of Bcl-2 and cyclin D1 was decreased and PTEN was increased in cells exposed to metformin. Metformin 111-120 BCL2 apoptosis regulator Homo sapiens 34-39 24858012-8 2014 In MCF-7 cells metformin decreased the activation of IRbeta, Akt and ERK1/2, increased p-AMPK, FOXO3a, p27, Bax and cleaved caspase-3, and decreased phosphorylation of p70S6K and Bcl-2 protein expression. Metformin 15-24 BCL2 apoptosis regulator Homo sapiens 179-184 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 BCL2 apoptosis regulator Homo sapiens 104-109 24378094-10 2013 Western blotting results revealed that the expression of CD133, phosphorylated Akt and the Bcl-2/Bax ratio were downregulated, and PTEN was upregulated in the Huh-7 cells after treated with 25 mmol/L metformin for 48 hrs. Metformin 200-209 BCL2 apoptosis regulator Homo sapiens 91-96 23803693-3 2013 Treatment of Panc1, L3.6pL and Panc28 pancreatic cancer cells with metformin downregulated Sp1, Sp3 and Sp4 proteins and several pro-oncogenic Sp-regulated genes including bcl-2, survivin, cyclin D1, vascular endothelial growth factor and its receptor, and fatty acid synthase. Metformin 67-76 BCL2 apoptosis regulator Homo sapiens 172-177 24577086-8 2014 Mechanistically, signal transducer and activator of transcription 3 (Stat3) and its downstream target Bcl-2 was inactivated by metformin treatment. Metformin 127-136 BCL2 apoptosis regulator Homo sapiens 102-107 24577086-10 2014 Similarly, the Bcl-2 proto-oncogene, an inhibitor of both apoptosis and autophagy, was repressed by metformin. Metformin 100-109 BCL2 apoptosis regulator Homo sapiens 15-20 24577086-11 2014 Ectopic expression of Bcl-2 protected cells from metformin-mediated autophagy and apoptosis. Metformin 49-58 BCL2 apoptosis regulator Homo sapiens 22-27 24577086-12 2014 In vivo, metformin downregulated Stat3 activity and Bcl-2 expression, induced apoptosis and autophagy, and inhibited tumor growth. Metformin 9-18 BCL2 apoptosis regulator Homo sapiens 52-57 24577086-13 2014 Together, inactivation of Stat3-Bcl-2 pathway contributes to metformin-induced growth inhibition of ESCC by facilitating crosstalk between apoptosis and autophagy. Metformin 61-70 BCL2 apoptosis regulator Homo sapiens 32-37 21388661-4 2011 Modulation of protein expression of the Bcl-2 family after treatment with metformin and/or cisplatin was determined by Western blotting. Metformin 74-83 BCL2 apoptosis regulator Homo sapiens 40-45 23151022-12 2012 In addition, metformin induced apoptosis in OSCC cells, significantly down-regulating the anti-apoptotic proteins Bcl-2 and Bcl-xL and up-regulating the pro-apoptotic protein Bax. Metformin 13-22 BCL2 apoptosis regulator Homo sapiens 114-119 21388661-6 2011 Moreover, we established that metformin can induce apoptosis in OVCAR-3 and OVCAR-4 cells by activating caspases 3/7, down-regulating Bcl-2 and Bcl-xL expression, and up-regulating Bax and Bad expression. Metformin 30-39 BCL2 apoptosis regulator Homo sapiens 134-139 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 BCL2 apoptosis regulator Homo sapiens 258-263 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 BCL2 apoptosis regulator Homo sapiens 258-263 34573418-7 2021 Overexpression of G0S2 significantly induced apoptosis of macrophages in a dose-dependent manner and blunted the function of the crucial anti-apoptotic gene Bcl-2, which was significantly reduced by metformin. Metformin 199-208 BCL2 apoptosis regulator Homo sapiens 157-162 34607979-6 2021 Accordingly, the p27 and p21 promoter activities were enhanced while Bcl-2 and IL-6 activities were significantly reduced by metformin treatment. Metformin 125-134 BCL2 apoptosis regulator Homo sapiens 69-74 33752282-8 2021 The cell growth and Bcl-2 expression level suppressed under hypoxia were reversed with a decrease of the induced Hif-1alpha and Cav-1 levels after AMPK activation with metformin (1 mM) or phenformin (0.1 microM). Metformin 168-177 BCL2 apoptosis regulator Homo sapiens 20-25 34078517-3 2021 High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation. Metformin 22-31 BCL2 apoptosis regulator Homo sapiens 100-105 34078517-3 2021 High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation. Metformin 217-226 BCL2 apoptosis regulator Homo sapiens 100-105 34078517-3 2021 High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation. Metformin 318-327 BCL2 apoptosis regulator Homo sapiens 100-105 35079096-6 2022 Overexpression of anti-apoptotic Bcl-2 family members decrease both metformin effects. Metformin 68-77 BCL2 apoptosis regulator Homo sapiens 33-38 33652909-8 2021 The cell-based analysis further indicated that metformin treatment regulated p38/JNK pathway to reduce Cyclin D1 and Bcl-2 expressions. Metformin 47-56 BCL2 apoptosis regulator Homo sapiens 117-122 32792943-8 2020 The presence of metformin also sensitized NSCLC cells to celecoxib-induced apoptosis by activating caspase-9, -8, -3, and -7, upregulating the pro-apoptotic proteins Bad and Bax, and downregulating the antiapoptotic proteins Bcl-xl and Bcl-2. Metformin 16-25 BCL2 apoptosis regulator Homo sapiens 236-241 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 BCL2 apoptosis regulator Homo sapiens 106-111 33268288-9 2021 Moreover, western blotting assay revealed that metformin could decrease Hcy-induced expression of Bax and cleaved caspase3, and increase the expression of Bcl-2. Metformin 47-56 BCL2 apoptosis regulator Homo sapiens 155-160 31220411-3 2019 We found that metformin decreased the cell apoptosis rate and death, ratio of Bcl-2/Bax, and expression of NR2A and NR2B, and increased the expression of LC3 in Abeta25-35 -treated SH-SY5Y cells. Metformin 14-23 BCL2 apoptosis regulator Homo sapiens 78-83 32248666-13 2020 The AMPK/Erk signaling pathway experiments revealed that the upregulation of Bcl-2 induced by insulin through Erk phosphorylation was inhibited by metformin and that such inhibition could be mitigated by the inhibition of AMPK. Metformin 147-156 BCL2 apoptosis regulator Homo sapiens 77-82 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 BCL2 apoptosis regulator Homo sapiens 212-217 32258099-12 2020 Further study revealed that metformin may attenuate the phosphorylation of the Stat3 and the Bcl-2 expression, which was restored by IL-6 partly in EC109 cells but not HEECs. Metformin 28-37 BCL2 apoptosis regulator Homo sapiens 93-98 32258099-15 2020 Therefore, the Stat3/Bcl-2 pathway-mediated apoptosis underlies the cell-type-specific drug sensitivity, suggesting metformin possesses a therapeutic activity and selectivity on esophageal cancer. Metformin 116-125 BCL2 apoptosis regulator Homo sapiens 21-26 30720062-9 2019 Metformin altered apoptosis-associated signaling to downregulate the BAD phosphorylation and Bcl-2, pro-caspase-9, pro-caspase-3 and pro-caspase-7 expression, and to upregulate BAD, cytochrome c, and Apaf-1 proteins levels in AGS cells. Metformin 0-9 BCL2 apoptosis regulator Homo sapiens 93-98 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 BCL2 apoptosis regulator Homo sapiens 193-198 31014173-6 2019 Here we show that while metformin can significantly inhibit cell growth and induce apoptosis of OSCC cultured alone in a dose-dependent manner through activating p-AMPKT172 and modulating Bcl-2, Bax, and cleaved PARP. Metformin 24-33 BCL2 apoptosis regulator Homo sapiens 188-193 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 BCL2 apoptosis regulator Homo sapiens 113-118 30936596-9 2019 The induced apoptosis by 2DG raised by metformin and the combination modulated the expression of Bcl-2 protein in all cell lines and it was more effective in TE11 cell line. Metformin 39-48 BCL2 apoptosis regulator Homo sapiens 97-102 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 BCL2 apoptosis regulator Homo sapiens 67-72 30088260-14 2018 Finally, we found that metformin may modulate the pro-apoptotic Bax, anti-apoptotic Bcl-2, MMP-2, MMP-9, miR-21 and miR-155 expression levels. Metformin 23-32 BCL2 apoptosis regulator Homo sapiens 84-89 30625181-6 2019 Similarly, metformin treatment suppressed expressions of anti-apoptotic genes BCL2 and Bcl-xL, and mesenchymal genes vimentin, N-cadherin, Zeb1 and Zeb2 with simultaneous enhancement of apoptotic caspase 3 and Bax, and epithelial genes E-cadherin and keratin 19 expressions, confirming an inhibitory effect of metformin in tumorigenesis. Metformin 11-20 BCL2 apoptosis regulator Homo sapiens 78-82 30625181-9 2019 Similarly, cholesterol treatment inverted metformin-reduced several gene expressions (e.g., Bcl-xL, BCL2, Zeb1, vimentin, and BMI-1). Metformin 42-51 BCL2 apoptosis regulator Homo sapiens 100-104 29765528-0 2018 Metabolic changes associated with metformin potentiates Bcl-2 inhibitor, Venetoclax, and CDK9 inhibitor, BAY1143572 and reduces viability of lymphoma cells. Metformin 34-43 BCL2 apoptosis regulator Homo sapiens 56-61 29399562-5 2018 In addition, mRNA expression of pro-apoptotic genes, p21 and Bax, was decreased and of anti-apoptotic genes, Bcl-2 and Bcl-xl, was increased with metformin treatment compared to QUIN-induced cells. Metformin 146-155 BCL2 apoptosis regulator Homo sapiens 109-114 28964970-5 2017 Mechanistically, metformin altered UPR activated by bortezomib, leading to a reduced expression of BiP, up-regulation of CHOP and down-regulation of Bcl-2. Metformin 17-26 BCL2 apoptosis regulator Homo sapiens 149-154 29344202-8 2017 The present study demonstrated that expression of p-ERK1/2, VEGF, VEGFR2 and Bcl-2 was downregulated by treatment with increasing concentrations of metformin, whereas expression of Bax and caspase-3 was evidently upregulated. Metformin 148-157 BCL2 apoptosis regulator Homo sapiens 77-82 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 BCL2 apoptosis regulator Homo sapiens 116-121