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作者

Zhang X.-Z. Guo A.-J. Lian L.-H. Jiang H.-X. Shi R.-J.

作者单位

School of Biological Science, Taishan Medical University, Taian Shandong 271016, China Dept. of Radiology, Taian Central Hospital, Taian Shandong 271000, China

刊名

Chinese Pharmacological Bulletin

年份

2012

卷号

Vol.28 No.2

页码

185-189

ISSN

1001-1978

关键词

BEZ235 Cell cycle Cell proliferation Doxorubicin hydrochloride PI3K/Akt β-catenin

摘要

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--2,5-diphenyl tetrazolium bromide assay. Cell cycle was analyzed by flow cytometry. Annexin V-FITC apoptosis detection kit was used to detect cell apoptosis. P...更多

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--2,5-diphenyl tetrazolium bromide 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 co-treatment with adriamycin substantially increased cytotoxic effects of adriamycin in hepatoma cells. Conclusions: The PI3K/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.收起

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