title: Metformin sensitizes hepatocellular carcinoma to arsenic trioxide-induced apoptosis by downregulating Bcl2 expression.
abstract: Hepatocellular carcinoma (HCC) is a highly malignant tumor that can evolve rapidly to acquire resistance to conventional chemotherapies. Arsenic trioxide (ATO) is a traditional Asian medicine, and a phase II study has shown that treatment with ATO alone was not effective against HCC. Bcl2 is an antiapoptotic protein that regulates chemotherapy in HCC. 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. In the present study, we used metformin and ATO alone or in combination and then tested proliferation, apoptosis, and Bcl2 level of HCC cells. The results showed that metformin enhanced both the proliferation-inhibiting and apoptosis-inducing effects of ATO on HCC cell lines HepG2 and BEL7402. Furthermore, this activity proceeded via a mechanism involving metformin-induced downregulation of Bcl2. A combination of ATO and metformin is therefore a potentially promising approach for HCC therapy.
authors.affiliation: Dalian Medical University, 9 Lvshunnan Road, Dalian, 116044, Liaoning, China, 13644986875@163.com.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Yang
authors.forename: Deguang
authors.initials: D
authors.lastname: Sun
authors.forename: Yu
authors.initials: Y
authors.lastname: Tian
authors.forename: Sunbin
authors.initials: S
authors.lastname: Ling
authors.forename: Liming
authors.initials: L
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008687:Metformin / Q000008:administration & dosage*; D010087:Oxides / Q000008:administration & dosage; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*
chemical_list: D001152:Arsenicals; D010087:Oxides; D019253:Proto-Oncogene Proteins c-bcl-2; D008687:Metformin; D000077237:Arsenic Trioxide