PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 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 mitogen-activated protein kinase 3 Homo sapiens 38-44 34004440-4 2021 Here, we show that metformin attenuated human soluble BAFF (hsBAFF)-induced cell proliferation and survival by blocking the Erk1/2 pathway in normal and B-lymphoid (Raji) cells. Metformin 19-28 mitogen-activated protein kinase 3 Homo sapiens 124-130 33007330-8 2021 Combination of NT157 with metformin induced enhanced inhibition of p-IGF1R, p-ERK1/2 and p-mTOR. Metformin 26-35 mitogen-activated protein kinase 3 Homo sapiens 78-84 34004440-5 2021 Pretreatment with U0126, knockdown of Erk1/2, or expression of dominant negative MKK1 strengthened metformin"s inhibition of hsBAFF-activated Erk1/2 and B-cell proliferation/viability, whereas expression of constitutively active MKK1 rendered high resistance to metformin. Metformin 99-108 mitogen-activated protein kinase 3 Homo sapiens 38-44 34004440-5 2021 Pretreatment with U0126, knockdown of Erk1/2, or expression of dominant negative MKK1 strengthened metformin"s inhibition of hsBAFF-activated Erk1/2 and B-cell proliferation/viability, whereas expression of constitutively active MKK1 rendered high resistance to metformin. Metformin 99-108 mitogen-activated protein kinase 3 Homo sapiens 142-148 34004440-6 2021 Further investigation found that overexpression of wild type PTEN or ectopic expression of dominant negative Akt potentiated metformin"s suppression of hsBAFF-induced Erk1/2 activation and proliferation/viability in Raji cells, implying a PTEN/Akt-dependent mechanism involved. Metformin 125-134 mitogen-activated protein kinase 3 Homo sapiens 167-173 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 mitogen-activated protein kinase 3 Homo sapiens 146-152 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 mitogen-activated protein kinase 3 Homo sapiens 66-72 32872293-0 2020 Metformin Derivative HL156A Reverses Multidrug Resistance by Inhibiting HOXC6/ERK1/2 Signaling in Multidrug-Resistant Human Cancer Cells. Metformin 0-9 mitogen-activated protein kinase 3 Homo sapiens 78-84 33489797-10 2020 Mechanistically, metformin extensively dephosphorylates Nrf2 by attenuating the interaction between Nrf2 and extracellular signal-regulated kinases 1/2 (ERK1/2), which then restores its polyubiquitination and accelerates its proteasomal degradation. Metformin 17-26 mitogen-activated protein kinase 3 Homo sapiens 153-159 30911317-10 2019 In addition, phosphorylated Erk1/2 was decreased while phosphorylated Akt was increased in metformin treatment. Metformin 91-100 mitogen-activated protein kinase 3 Homo sapiens 28-34 32460900-9 2020 We further show that this increase is associated with elevated ERK1/2 and Akt signalling and can be rescued by metformin treatment. Metformin 111-120 mitogen-activated protein kinase 3 Homo sapiens 63-69 31789625-9 2020 Metformin downregulated the levels of p-NF-kappaB p65, p-Erk1/2, p-AKT, and p-mTOR proteins. Metformin 0-9 mitogen-activated protein kinase 3 Homo sapiens 57-63 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 mitogen-activated protein kinase 3 Homo sapiens 125-129 30911317-11 2019 Taken together, these findings suggest that metformin promotes neuronal differentiation via ROS activation through Cdk5/Sox6 crosstalk, relating to Erk1/2 and Akt signaling. Metformin 44-53 mitogen-activated protein kinase 3 Homo sapiens 148-154 30333878-8 2018 Furthermore, in the presence of metformin, inhibitors of the p38 MAPK and JNK signaling pathway at different concentrations did not affect the levels of Nrf2, but inhibitors of the Akt and ERK1/2 pathway at different doses reduced the expression of Nrf2. Metformin 32-41 mitogen-activated protein kinase 3 Homo sapiens 65-69 30680029-7 2019 VPC23019 and U0126 eliminated the neuroprotective effects of metformin on neuronal apoptosis, which suggests that metformin is able to protect against sevoflurane-induced neurotoxicity via activation of the S1P1-dependent ERK1/2 signaling pathway. Metformin 114-123 mitogen-activated protein kinase 3 Homo sapiens 222-226 30680029-0 2019 Metformin protects against sevoflurane-induced neuronal apoptosis through the S1P1 and ERK signaling pathways. Metformin 0-9 mitogen-activated protein kinase 3 Homo sapiens 87-90 30680029-6 2019 The current study revealed that metformin may reduce sevoflurane-induced neuronal apoptosis via activating mitogen-activated protein kinase (ERK)1/2 phosphorylation. Metformin 32-41 mitogen-activated protein kinase 3 Homo sapiens 141-148 30680029-7 2019 VPC23019 and U0126 eliminated the neuroprotective effects of metformin on neuronal apoptosis, which suggests that metformin is able to protect against sevoflurane-induced neurotoxicity via activation of the S1P1-dependent ERK1/2 signaling pathway. Metformin 61-70 mitogen-activated protein kinase 3 Homo sapiens 222-226 30333878-9 2018 In addition, inhibitors of p38 MAPK and JNK did not affect the effect of metformin on Nrf2, while inhibitors of Akt and ERK1/2 dose-dependently enhanced the inhibitory effects of metformin in A549 cells. Metformin 179-188 mitogen-activated protein kinase 3 Homo sapiens 31-35 30333878-9 2018 In addition, inhibitors of p38 MAPK and JNK did not affect the effect of metformin on Nrf2, while inhibitors of Akt and ERK1/2 dose-dependently enhanced the inhibitory effects of metformin in A549 cells. Metformin 179-188 mitogen-activated protein kinase 3 Homo sapiens 120-126 30333878-10 2018 In conclusion, metformin inhibits the phosphoinositide-3 kinase/Akt and ERK1/2 signaling pathways in A549 cells to reduce the expression of Nrf2, GSTA1 and ABCC1. Metformin 15-24 mitogen-activated protein kinase 3 Homo sapiens 72-78 29760016-7 2018 When applied to cultured cardiomyocytes, insulin and metformin increased titin phosphorylation at S4010, S4099, and S11878 via enhanced ERK1/2 (extracellular signal regulated kinase 1/2) and PKCalpha (protein kinase Calpha) activity; NRG-1 application enhanced ERK1/2 activity but reduced PKCalpha activity. Metformin 53-62 mitogen-activated protein kinase 3 Homo sapiens 136-142 29380373-11 2018 In vitro studies confirmed that metformin inhibited TGF-beta1 induced inflammatory and fibrotic responses through Smad3, ERK1/2, and P38 pathways in human renal proximal tubular cells. Metformin 32-41 mitogen-activated protein kinase 3 Homo sapiens 121-127 29760016-7 2018 When applied to cultured cardiomyocytes, insulin and metformin increased titin phosphorylation at S4010, S4099, and S11878 via enhanced ERK1/2 (extracellular signal regulated kinase 1/2) and PKCalpha (protein kinase Calpha) activity; NRG-1 application enhanced ERK1/2 activity but reduced PKCalpha activity. Metformin 53-62 mitogen-activated protein kinase 3 Homo sapiens 261-267 29415987-8 2018 Mechanistically, both HSP60 knockdown and oxidative phosphorylation (OXPHOS) inhibition by metformin decreased Erk1/2 phosphorylation and induced apoptosis and cell cycle arrest, whereas Erk1/2 reactivation with EGF promoted cell proliferation. Metformin 91-100 mitogen-activated protein kinase 3 Homo sapiens 111-117 29635803-12 2018 Metformin maintained high activation of AMPK and decreased ERK1/2 levels after HF in both cell lines and only after HI in PNT1A, which was able to decrease the cell proliferation triggered by these treatments. Metformin 0-9 mitogen-activated protein kinase 3 Homo sapiens 59-65 29549478-0 2018 Metformin Promotes HaCaT Cell Apoptosis through Generation of Reactive Oxygen Species via Raf-1-ERK1/2-Nrf2 Inactivation. Metformin 0-9 mitogen-activated protein kinase 3 Homo sapiens 96-102 29472557-6 2018 Metformin reduced cyclin D1 expression and RB, STAT3, STAT5, ERK1/2 and p70S6K phosphorylation. Metformin 0-9 mitogen-activated protein kinase 3 Homo sapiens 61-67 29415987-11 2018 Thus, our findings indicate for the first time that HSP60 may serve as a novel diagnostic target of human pancreatic cancer, and that inhibition of mitochondrial function using drugs such as metformin may be a beneficial therapeutic strategy targeting pancreatic cancer cells with aberrant function of the HSP60/OXPHOS/Erk1/2 phosphorylation axis. Metformin 191-200 mitogen-activated protein kinase 3 Homo sapiens 319-325 29399562-6 2018 The immunoreactivity of phosphorylated ERK1/2 was elevated in cells treated with metformin, indicating the ERK1/2 signaling pathway in the neuroprotective effects of metformin in QUIN-induced cell death. Metformin 81-90 mitogen-activated protein kinase 3 Homo sapiens 39-45 29399562-6 2018 The immunoreactivity of phosphorylated ERK1/2 was elevated in cells treated with metformin, indicating the ERK1/2 signaling pathway in the neuroprotective effects of metformin in QUIN-induced cell death. Metformin 81-90 mitogen-activated protein kinase 3 Homo sapiens 107-113 29399562-6 2018 The immunoreactivity of phosphorylated ERK1/2 was elevated in cells treated with metformin, indicating the ERK1/2 signaling pathway in the neuroprotective effects of metformin in QUIN-induced cell death. Metformin 166-175 mitogen-activated protein kinase 3 Homo sapiens 39-45 29399562-6 2018 The immunoreactivity of phosphorylated ERK1/2 was elevated in cells treated with metformin, indicating the ERK1/2 signaling pathway in the neuroprotective effects of metformin in QUIN-induced cell death. Metformin 166-175 mitogen-activated protein kinase 3 Homo sapiens 107-113 29399562-7 2018 Collectively, our data demonstrates that metformin exerts its neuroprotective effects by inhibiting intracellular calcium increases, allowing it to regulate ERK1/2 signaling and modulate cell survival and death genes. Metformin 41-50 mitogen-activated protein kinase 3 Homo sapiens 157-163 28927780-7 2017 Metformin inhibited ERK1/2, JNK, and PI3K/Akt, but activated p38 pathway in these two cells. Metformin 0-9 mitogen-activated protein kinase 3 Homo sapiens 20-26 29344202-0 2017 Metformin in combination with cisplatin inhibits cell viability and induces apoptosis of human ovarian cancer cells by inactivating ERK 1/2. Metformin 0-9 mitogen-activated protein kinase 3 Homo sapiens 132-139 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 mitogen-activated protein kinase 3 Homo sapiens 52-58 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 237-246 mitogen-activated protein kinase 3 Homo sapiens 42-48 26675396-13 2015 Metformin could enhance the EGFR signaling pathway inhibitor AG1478 inhibition of endometrial cancer cells, which may inhibit EGFR expression of phosphorylated proteins to inhibit the phosphorylation of ERK1/2 proteins and then inhibit proliferation of endometrial cancer cells. Metformin 0-9 mitogen-activated protein kinase 3 Homo sapiens 203-209 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 mitogen-activated protein kinase 3 Homo sapiens 442-448 26824324-0 2016 Metformin inhibits 17beta-estradiol-induced epithelial-to-mesenchymal transition via betaKlotho-related ERK1/2 signaling and AMPKalpha signaling in endometrial adenocarcinoma cells. Metformin 0-9 mitogen-activated protein kinase 3 Homo sapiens 104-110 26824324-5 2016 In addition, metformin increased the expression of betaKlotho, a fibroblast growth factors (FGFs) coreceptor, and decreased ERK1/2 phosphorylation in both Ishikawa and KLE cells. Metformin 13-22 mitogen-activated protein kinase 3 Homo sapiens 124-130 26824324-9 2016 In conclusion, metformin abolishes 17beta-estradiol-induced cell proliferation and EMT in endometrial adenocarcinoma cells by upregulating betaKlotho expression, inhibiting ERK1/2 signaling, and activating AMPKalpha signaling. Metformin 15-24 mitogen-activated protein kinase 3 Homo sapiens 173-179 26804175-8 2016 Importantly, the Runx2 knockdown in bone-derived cells resulted in increased sensitivity to both Erk1/2 inhibition and AMPKalpha activation by PD184161 and metformin, respectively, despite increased IGF-1Rbeta and AMPKalpha levels. Metformin 156-165 mitogen-activated protein kinase 3 Homo sapiens 97-103 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 mitogen-activated protein kinase 3 Homo sapiens 69-75 25862373-10 2015 IGF-1 activated both ERK1/2 and Akt, but these effects were attenuated by metformin treatment. Metformin 74-83 mitogen-activated protein kinase 3 Homo sapiens 21-27 25245054-5 2014 Metformin was also found to significantly inhibit the expression and secretion of MMP-9 and uPA in HCC cells, and suppress the phosphorylation of ERK1/2 and JNK1/2. Metformin 0-9 mitogen-activated protein kinase 3 Homo sapiens 146-152 25245054-6 2014 Treatment with an ERK1/2 inhibitor (PD98059) or JNK1/2 inhibitor (SP600125) enhanced the inhibitory effects of metformin on the migration and invasion of HCC cells. Metformin 111-120 mitogen-activated protein kinase 3 Homo sapiens 18-24 25491250-11 2014 Preliminary analysis of total AKT and ERK1/2 levels in plasma EVs from patients with NSCLC before and after sorafenib/metformin treatment (n=12) shows a significant decrease in AKT levels among patients with a favourable treatment response (p<0.005). Metformin 118-127 mitogen-activated protein kinase 3 Homo sapiens 38-44 24858012-11 2014 Treatment with metformin resulted in an increase in p-p38 MAPK, catalase, MnSOD and Cu/Zn SOD protein expression. Metformin 15-24 mitogen-activated protein kinase 3 Homo sapiens 58-62 24419232-8 2014 Metformin inhibits VEGF-dependent activation of extracellular signal-regulated kinase 1/2, and the inhibition of AMPK activity abrogates this event. Metformin 0-9 mitogen-activated protein kinase 3 Homo sapiens 48-89 19574398-9 2009 Involvement of the ERK signaling pathway was demonstrated by the significant increase in phosphorylated ERK-1,2 with the combined metformin and insulin treatment. Metformin 130-139 mitogen-activated protein kinase 3 Homo sapiens 104-111 24396411-0 2014 Metformin inhibits proliferation of human keratinocytes through a mechanism associated with activation of the MAPK signaling pathway. Metformin 0-9 mitogen-activated protein kinase 3 Homo sapiens 110-114 24396411-11 2014 In conclusion, metformin treatment upregulated the levels of p-AMPK and p-ERK1/2 in HaCaT cells, and significantly inhibited HaCaT cell proliferation in vitro by a mechanism associated with activation of the mitogen-activated protein kinase signaling pathway. Metformin 15-24 mitogen-activated protein kinase 3 Homo sapiens 74-80 23362830-4 2013 Metformin treatment decreased cellular TP and ERCC1 protein and mRNA levels by down-regulating phosphorylated MEK1/2-ERK1/2 protein levels in a dose- and time-dependent manner. Metformin 0-9 mitogen-activated protein kinase 3 Homo sapiens 117-123 20371705-7 2010 Although metformin did not inhibit the activation of either nuclear factor-kappaB or activator protein-1, it inhibited the expression of early growth response factor-1 (Egr-1) and phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2 in monocytes stimulated with LPS or oxLDL. Metformin 9-18 mitogen-activated protein kinase 3 Homo sapiens 199-254 15983226-9 2005 Treatment of HASMCs with metformin decreased leptin-induced ROS production and activation of PKC, ERK1/2, and NF-kappaB. Metformin 25-34 mitogen-activated protein kinase 3 Homo sapiens 98-104 16564524-7 2006 These results show for the first time a direct osteogenic effect of metformin on osteoblasts in culture, which could be mediated by activation/redistribution of ERK-1/2 and induction of e/iNOS. Metformin 68-77 mitogen-activated protein kinase 3 Homo sapiens 161-168 19414528-0 2009 Metformin decreases angiogenesis via NF-kappaB and Erk1/2/Erk5 pathways by increasing the antiangiogenic thrombospondin-1. Metformin 0-9 mitogen-activated protein kinase 3 Homo sapiens 51-57 19414528-8 2009 In vitro migration and angiogenesis were significantly increased in serum from PCOS women (P < 0.01); these effects were significantly attenuated by metformin treatment (P < 0.01) through the regulation of TSP-1 levels via nuclear factor-kappaB (NF-kappaB), extracellular regulated-signal kinase 1/2 (Erk1/2) and Erk5 pathways. Metformin 152-161 mitogen-activated protein kinase 3 Homo sapiens 307-313 35561893-12 2022 Moreover, metformin activated the EPCR, ERK 1/2, p38 MAPK and NF-kappaB pathways but miR-532 mimic suppressed the activation of pathways. Metformin 10-19 mitogen-activated protein kinase 3 Homo sapiens 40-47