中国药理学通报2012，Vol.28Issue(2)：185-189,5.DOI:10.3969/j.issn.1001-1978.2012.02.009
PI3K/mTOR抑制剂BEZ235抑制HepG2细胞增殖及与阿霉素的协同效应
The inhibitory effect of BEZ235,an inhibitor of phosphoinositol-3-kinase/mTOR,on HepG2 cell proliferation and its synergic effect in combination with adriamycin
摘要
Abstract
Aim To detect the effect of BEZ235 , inhibitor of phosphoinositol-3-kinase/Akt and mammalian target of rapamycin, on the cell proliferation and apoptosis in human hepatoma cancer cell line HepG2 cells, and also to investigate the synergistic effect of BEZ235 combined with adriamycin on HepG2 cells. Methods Cell growth was detected by 3-( 4,5-dimethylthiazol-2-y1 )-2,5-diphenyl tetrazolium bromide ( MTT ) assay. Cell cycle was analyzed by flow cytometry. Annexin V -FITC apoptosis detection kit was used to detect cell apoptosis. Protein expression was examined by Western blot analysis. Results Cell proliferation was inhibited in dose-and time-dependent manner when HepG2 cells were treated with 2.5 μmol · L-1 ~ 7. 5 μmol · L-1 BEZ235. Flow cytometry results indicated that BEZ235 arrested cell cycle progression at the G1 phase via downregulating the expression of cyclinD1. BEZ235 cotreatment with adriamycin substantially increased cyto-toxic effects of adriamycin in hepatoma cells. Conclusions The PDK/mTOR dual inhibitor BEZ235 shows substantial anti-tumor activity in human hepatocelluar carcinoma cell line HepG2, and down-regulates the expression of β-catenin which probably is the potential mechanism for the synergistic effect of BEZ235 and adriamycin in hepatocellular carcinoma.关键词
BEZ235/PI3K/Akt/细胞增殖/细胞周期/阿霉素/β-cateninKey words
BEZ235/ PDK/Akt/ cell proliferation/ cell cycle/ doxorubicin hydrochloride/ β-catenin分类
医药卫生引用本文复制引用
张显忠,郭爱军,廉立慧,姜红霞,史仁玖..PI3K/mTOR抑制剂BEZ235抑制HepG2细胞增殖及与阿霉素的协同效应[J].中国药理学通报,2012,28(2):185-189,5.基金项目
国家自然科学基金项目资助(No 30800422) （No 30800422）
