PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 27305912-9 2017 RESULTS: After adjusting for multiple comparisons in the 32 tumors from metformin-treated patients vs. 34 untreated historical controls, 11 proteins were significantly different between cases vs. CONTROLS: increases in Raptor, C-Raf, Cyclin B1, Cyclin D1, TRFC, and Syk; and reductions in pMAPKpT202,Y204, JNKpT183,pT185, BadpS112, PKC.alphapS657, and SrcpY416. Metformin 72-81 cyclin D1 Homo sapiens 245-254 27305912-10 2017 Cyclin D1 change after metformin by IHC was not observed. Metformin 23-32 cyclin D1 Homo sapiens 0-9 27128966-0 2017 Metformin induces degradation of cyclin D1 via AMPK/GSK3beta axis in ovarian cancer. Metformin 0-9 cyclin D1 Homo sapiens 33-42 27128966-3 2017 Here, we first describe that the anti-cancer effect of metformin is mediated by cyclin D1 deregulation via AMPK/GSK3beta axis in ovarian cancer cells. Metformin 55-64 cyclin D1 Homo sapiens 80-89 27128966-5 2017 Metformin induced the G1 cell cycle arrest, in parallel with a decrease in the protein expressions of cyclin D1 without affecting its transcriptional levels. Metformin 0-9 cyclin D1 Homo sapiens 102-111 27128966-6 2017 Using a proteasomal inhibitor, we could address that metformin-induced decrease in cyclin D1 through the ubiquitin/proteasome process. Metformin 53-62 cyclin D1 Homo sapiens 83-92 27128966-7 2017 Cyclin D1 degradation by metformin requires the activation of GSK3beta, as determined based on the treatment with GSK3beta inhibitors. Metformin 25-34 cyclin D1 Homo sapiens 0-9 27128966-9 2017 These findings suggested that the anticancer effects of metformin was induced due to cyclin D1 degradation via AMPK/GSK3beta signaling axis that involved the ubiquitin/proteasome pathway specifically in ovarian cancer cells. Metformin 56-65 cyclin D1 Homo sapiens 85-94 28045889-11 2017 It was shown that metformin downregulates the expression of cyclin D1 and increases the p27KIP1 level. Metformin 18-27 cyclin D1 Homo sapiens 60-69 27779693-5 2016 Metformin upregulated the expression of p21Waf1 and p27kip1, and downregulated the expression of cyclin D1, a key protein required for cell cycle progression. Metformin 0-9 cyclin D1 Homo sapiens 97-106 27779693-7 2016 Administration of metformin enhanced the efficacy of gemcitabine and cisplatin to suppress the growth of cholangiocarcinoma tumors established in experimental models by inhibiting cell proliferation and inducing cell apoptosis through their effects on AMPK, cyclin D1 and caspase-3. Metformin 18-27 cyclin D1 Homo sapiens 258-267 26986571-6 2016 Metformin repressed E2-inducible estrogen response element (ERE) luciferase activity, protein levels and mRNA levels of E2/ERalpha-regulated genes [including c-Myc, cyclin D1, progesterone receptor (PR) and pS2] to a greater degree than tamoxifen, resulting in inhibition of cell proliferation of MCF-7, TR MCF-7 and MDA-MB-361 cells. Metformin 0-9 cyclin D1 Homo sapiens 165-174 26398221-5 2015 Metformin treatment also led to marked decreases in cyclin D1 and cyclin-dependent kinase (Cdk) 4 protein levels and retinoblastoma protein phosphorylation. Metformin 0-9 cyclin D1 Homo sapiens 52-61 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 cyclin D1 Homo sapiens 0-9 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 cyclin D1 Homo sapiens 156-165 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 cyclin D1 Homo sapiens 94-102 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 cyclin D1 Homo sapiens 32-40 25305450-6 2015 Western blot showed that metformin activated caspase 3, caspase 9, PARP-1, Bak, and p21 and inactivated Mcl-1, HIAP-1, cyclin D1, CDK4, and CDK6. Metformin 25-34 cyclin D1 Homo sapiens 119-128 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 cyclin D1 Homo sapiens 44-53 24351837-4 2013 Metformin significantly inhibited the proliferation and colony formation of 5637 and T24 cells in vitro; specifically, metformin induced an apparent cell cycle arrest in G0/G1 phases, accompanied by a strong decrease of cyclin D1, cyclin-dependent kinase 4 (CDK4), E2F1 and an increase of p21waf-1. Metformin 119-128 cyclin D1 Homo sapiens 220-229 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 cyclin D1 Homo sapiens 198-207 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 cyclin D1 Homo sapiens 189-198 24008375-0 2013 Metformin suppresses hepatocellular carcinoma cell growth through induction of cell cycle G1/G0 phase arrest and p21CIP and p27KIP expression and downregulation of cyclin D1 in vitro and in vivo. Metformin 0-9 cyclin D1 Homo sapiens 164-173 24008375-13 2013 Treatment with metformin upregulated the expression of p21CIP and p27KIP, but downregulated cyclin D1 levels, both in vitro and in vivo. Metformin 15-24 cyclin D1 Homo sapiens 92-101 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 cyclin D1 Homo sapiens 234-243 23229592-10 2013 Metformin inhibited the growth of three ESCC cell lines, and this inhibition may have involved reductions in cyclin D1, Cdk4 and Cdk6. Metformin 0-9 cyclin D1 Homo sapiens 109-118 21676631-7 2013 Moreover, metformin down-regulated cyclin D1 expression and induced G0/G1 cell cycle arrest in these cells. Metformin 10-19 cyclin D1 Homo sapiens 35-44 23151022-11 2012 Metformin treatment led to a remarkable decrease of cyclin D1, cyclin-dependent kinase (CDK) 4 and CDK6 protein levels and phosphorylation of retinoblastoma protein, but did not affect p21 or p27 protein expression in OSCC cells. Metformin 0-9 cyclin D1 Homo sapiens 52-61 23151022-13 2012 Metformin also markedly reduced the expression of cyclin D1 and increased the numbers of apoptotic cells in vivo, thus inhibiting the growth of OSCC xenografts. Metformin 0-9 cyclin D1 Homo sapiens 50-59 22389381-6 2012 We found that metformin inhibited growth and decreased expression of cyclin D1 in MTC cells. Metformin 14-23 cyclin D1 Homo sapiens 69-78 21717584-4 2011 Further studies revealed that the protein level of cyclin D1 decreased and the percentage of the cells in G0/G1 phase increased by 5 mM metformin treatment. Metformin 136-145 cyclin D1 Homo sapiens 51-60 21717584-7 2011 In a summary, metformin prevents proliferation of C666-1 cells by down-regulating cyclin D1 level and inducing G1 cell cycle arrest. Metformin 14-23 cyclin D1 Homo sapiens 82-91 20813708-6 2010 The expression of cyclin D1 in metformin-treated cells were lowered significantly as compared with that in the control cells. Metformin 31-40 cyclin D1 Homo sapiens 18-27 20813708-7 2010 Telomerase activity was also decreased significantly in the cells after treatment with 5 mmol/L metformin for 72 h. CONCLUSION: Metformin can inhibit the growth of SW-480 cells mainly by blocking the cell cycle at G0/G1, down-regulating the expression of cyclin D1 and decreasing telomerase activity. Metformin 96-105 cyclin D1 Homo sapiens 255-264 20813708-7 2010 Telomerase activity was also decreased significantly in the cells after treatment with 5 mmol/L metformin for 72 h. CONCLUSION: Metformin can inhibit the growth of SW-480 cells mainly by blocking the cell cycle at G0/G1, down-regulating the expression of cyclin D1 and decreasing telomerase activity. Metformin 128-137 cyclin D1 Homo sapiens 255-264 19440038-7 2009 At the molecular level, metformin increases P-AMPK, reduces P-EGFR, EGFR, P-MAPK, P-Src, cyclin D1 and cyclin E (but not cyclin A or B, p27 or p21), and induces PARP cleavage in a dose- and time-dependent manner. Metformin 24-33 cyclin D1 Homo sapiens 89-98 19221498-6 2009 At the molecular level, metformin treatment was associated with a reduction of cyclin D1 and E2F1 expression with no changes in p27(kip1) or p21(waf1). Metformin 24-33 cyclin D1 Homo sapiens 79-88 19046439-0 2008 Cell cycle arrest in Metformin treated breast cancer cells involves activation of AMPK, downregulation of cyclin D1, and requires p27Kip1 or p21Cip1. Metformin 21-30 cyclin D1 Homo sapiens 106-115 19046439-8 2008 As in previous studies, metformin treatment led to activation of (AMPK) and downregulation of cyclin D1. Metformin 24-33 cyclin D1 Homo sapiens 94-103 19046439-13 2008 CONCLUSION: Cell cycle arrest in response to metformin requires CDK inhibitors in addition to AMPK activation and cyclin D1 downregulation. Metformin 45-54 cyclin D1 Homo sapiens 114-123 18212742-0 2008 The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Metformin 22-31 cyclin D1 Homo sapiens 104-113 18212742-10 2008 Similar, to the in vitro study, metformin led to a strong reduction of cyclin D1 protein level in tumors providing evidence for a mechanism that may contribute to the antineoplastic effects of metformin suggested by recent epidemiological studies. Metformin 32-41 cyclin D1 Homo sapiens 71-80 18212742-10 2008 Similar, to the in vitro study, metformin led to a strong reduction of cyclin D1 protein level in tumors providing evidence for a mechanism that may contribute to the antineoplastic effects of metformin suggested by recent epidemiological studies. Metformin 193-202 cyclin D1 Homo sapiens 71-80 34235153-9 2021 The in vitro results showed that the combination of metformin and pemetrexed exhibited an antiproliferative effect in reducing cell viability and colony formation, the downregulation of cyclin D1 and A2 and the upregulation of CDKN1B, which are involved in the G1/S phase. Metformin 52-61 cyclin D1 Homo sapiens 186-195 35264157-12 2022 Further study showed that metformin blocked the cells in G1 phase by inducing phosphorylated YAP1 and reducing the expression of cyclin D1, CDK6, CDK4 and RB, which enhanced the chemosensitivity of cisplatin and activated the expression of cleaved caspase 3 in TGCTs. Metformin 26-35 cyclin D1 Homo sapiens 129-138 35236827-6 2022 In mechanism, INHBA is an important ligand of TGF-beta signaling and metformin blocked the activation of TGF-beta signaling by targeting INHBA, and then down-regulated the activity of PI3K/Akt pathway, leading to the reduction of cyclinD1 and cell cycle arrest. Metformin 69-78 cyclin D1 Homo sapiens 230-238 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 cyclin D1 Homo sapiens 81-90 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 cyclin D1 Homo sapiens 106-115 33350292-7 2021 PBCCs treated with 25 mM metformin had lower cyclin D1 expression compared with non-treated cells, however, the difference was not statistically significant. Metformin 25-34 cyclin D1 Homo sapiens 45-54 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 cyclin D1 Homo sapiens 35-44 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 cyclin D1 Homo sapiens 103-112 31892560-8 2020 Immunohistochemical analysis of tumor tissues revealed down-regulation of cyclin D1 and proliferating cell nuclear antigen in the metformin-treated group. Metformin 130-139 cyclin D1 Homo sapiens 74-83 31744691-8 2019 Metformin promoted the expression of p-AMPK, P53, P21CIP1 and P27KIP1, while inhibited the expression of CDK4 and CyclinD1. Metformin 0-9 cyclin D1 Homo sapiens 114-122 31455378-6 2019 Western Blot was performed to detect the expressions of AMPKalpha, Yap1, CCND1, CCNE1/2 and CDK2/4/6 in the metformin-treated BLCA cell lines. Metformin 108-117 cyclin D1 Homo sapiens 73-78 31455378-12 2019 And metformin upregulated the phosphorylated AMPKalpha and decreased the expressions of Yap1 and CCND1, CCNE1/2 and CDK4/6. Metformin 4-13 cyclin D1 Homo sapiens 97-102 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 cyclin D1 Homo sapiens 20-29 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 cyclin D1 Homo sapiens 35-44 29920623-0 2018 Synergistic Anti-proliferative Effects of Metformin and Silibinin Combination on T47D Breast Cancer Cells via hTERT and Cyclin D1 Inhibition. Metformin 42-51 cyclin D1 Homo sapiens 120-129 29693804-0 2018 Synergistic Growth Inhibitory Effects of Chrysin and Metformin Combination on Breast Cancer Cells through hTERT and Cyclin D1 Suppression Objective: To explore the possibility of a novel chemopreventive strategy for improving breast cancer treatment,the anticancer effects of a combination two natural compounds, Chrysin and Metformin, against T47D breast cancercells were investigated. Metformin 53-62 cyclin D1 Homo sapiens 116-125 29693804-5 2018 Conclusion: The conmbinationof metformin and chrysin suppressing hTERT and cyclin D1 gene expression might offer an appropriate approach forbreast cancer therapy. Metformin 31-40 cyclin D1 Homo sapiens 75-84 29472557-6 2018 Metformin reduced cyclin D1 expression and RB, STAT3, STAT5, ERK1/2 and p70S6K phosphorylation. Metformin 0-9 cyclin D1 Homo sapiens 18-27 28440424-6 2017 Importantly, metformin reduced the expression of cyclin D1, cyclin E, cyclin-dependent kinase 4, and phosphorylated retinoblastoma protein, which resulted in cell cycle arrest at the G0/G1 phase. Metformin 13-22 cyclin D1 Homo sapiens 49-58 29871302-8 2017 The combination of metformin and 5-fluorouracil produced an antagonism action in Hep-2 cells.Western blot assay showed that metformin, cisplatin, 5-fluorouracil could have caused the increase of expression level of AMPK-alpha, P21 and Cyclin D1 in Hep-2 cells while Paclitaxel could have cause the decrease of expression level of Cyclin D1. Metformin 19-28 cyclin D1 Homo sapiens 235-244 29871302-8 2017 The combination of metformin and 5-fluorouracil produced an antagonism action in Hep-2 cells.Western blot assay showed that metformin, cisplatin, 5-fluorouracil could have caused the increase of expression level of AMPK-alpha, P21 and Cyclin D1 in Hep-2 cells while Paclitaxel could have cause the decrease of expression level of Cyclin D1. Metformin 19-28 cyclin D1 Homo sapiens 330-339 29871302-8 2017 The combination of metformin and 5-fluorouracil produced an antagonism action in Hep-2 cells.Western blot assay showed that metformin, cisplatin, 5-fluorouracil could have caused the increase of expression level of AMPK-alpha, P21 and Cyclin D1 in Hep-2 cells while Paclitaxel could have cause the decrease of expression level of Cyclin D1. Metformin 124-133 cyclin D1 Homo sapiens 235-244 29871302-8 2017 The combination of metformin and 5-fluorouracil produced an antagonism action in Hep-2 cells.Western blot assay showed that metformin, cisplatin, 5-fluorouracil could have caused the increase of expression level of AMPK-alpha, P21 and Cyclin D1 in Hep-2 cells while Paclitaxel could have cause the decrease of expression level of Cyclin D1. Metformin 124-133 cyclin D1 Homo sapiens 330-339 29871302-11 2017 Metformin has an antagonism on the anticancer effect to 5-fluorouracil in Hep-2 cells, and this antagonistic effect occurred partially through molecular signal pathways of AMPK-alpha, P21 and Cyclin D1 and it"s significantly related to the cell cycle arrest. Metformin 0-9 cyclin D1 Homo sapiens 192-201