一种新型PI3K/mTOR双抑制剂GDC-0941的抗肝癌机制探讨

目的 探讨磷脂酰肌醇3磷酸激酶(PI3K)/雷帕霉素靶蛋白(mTOR)激酶双抑制剂GDC-0941抗肝癌活性及其作用机制.方法 分别采用MTT法和流式细胞术测定GDC-0941对HepG2肝癌细胞生长和细胞周期的影响;通过免疫印迹法检测信号通路蛋白、细胞周期抑制因子和凋亡相关蛋白的表达.结果 GDC-0941对HepG...

The Antitumor Activity of PI3K/mTOR Dual Inhibitor GDC-0941 in HepG2 Cells

Objective To investigate the antitumor activity of PI3K/mTOR dual inhibitor GDC-0941 and its underlying mechanism in HepG2 cells.Methods MTT assay was performed for the cell growth inhibitory rate.Flow cytometric analysis was used to detect cell cycle progression.Western blot was performed to detect the expressions of signaling pathway proteins,cell cycle inhibitory proteins and apoptosis related proteins.Results A significant dose-dependent growth inhibition was observed in GDC-0941 treated cells,which was associated with G0/G1 phase arrest.GDC-0941 specifically abrogated phosphorylation of protein kinase B(Akt) and ribosomal protein S6 kinase 1(S6K1).Cell cycle inhibitors p21,p27 and apoptosis related proteins p53,bax,bad were upregulated,but anti-apoptosis protein bcl-2 was downregulated with GDC-0941 treatment.Conclusion GDC-0941 induced up-regulation of cell cycle inhibitors,pro-apoptosis proteins,and simultaneously down-regulation of anti-apoptosis protein,which finally induced cell growth inhibition and apoptosis in HepG2 cells.