Effect of AZD5363 on apoptosis and autophagy in hepatocellular carcinoma cells / 中国病理生理杂志

AIM:To investigate the effect of AZD5363, an inhibitor of Akt, on the viability, apoptosis and autophagy in human hepatocelluar carcinoma cells and the molecular mechanisms.METHODS:MTT assay was used to detect the cell viability.TUNEL assay was used to analysis the apoptosis.The expression of PARP and LC3-II proteins was examined by Western blot analysis.The autophagy was characterized by the expression and distribution of GFP-LC3.RE-SULTS:The results of MTT assay indicated that AZD5363 suppressed the cell viability in a dose-dependent manner (P<0.05).High doses of AZD5363 triggered apoptosis via activating the cleavage of PARP.AZD5363 treatment induced autophagy both in Hep G2 cells and Huh7 cells by increasing the level of LC3-II.Blockage of autophagy by chloroquine promoted AZD5363-induced apoptosis in the hepatocellular carcinoma cells.CONCLUSION:AZD5363 increased apoptosis and autophagy in Hep G2 cells and Huh7 cells.Blockage of autophagy magnified AZD5363-induced apoptosis in hepatocellular carcinoma cells.

AZD5363 inhibits cell proliferation, migration and induces apoptosis of breast cancer MDA-MB-231 cells / 肿瘤

Objective: To investigate the effects of AZD5363, an inhibitor of protein kinase B (Akt), on proliferation, migration and apoptosis of human breast cancer cell line MDA-MB-231, and to further clarify their possible molecular mechanisms Methods: After treatment with different concentrations (0.5, 1, 5, 10, 20 and 50 μmol/L) of AZD5363, the viability of MDA-MB-231 cells was detected by MTT assay, the cell cycle distribution was analyzed by FCM, the cell migration ability was detected by wound healing test and Transwell chamber assay, the cell apoptosis rate was detected by TUNEL method. Then the expression levels of cell cycle- and apoptosis-related proteins were measured by Western blotting. Results: AZD5363 suppressed the cell viability in a dose-dependent manner (P < 0.05), and arrested the cell cycle progression at S phase by up-regulating the expression of p53 and down-regulating the expression of cyclin B1 (all P < 0.05). AZD5363 significantly inhibited the cell migration (P < 0.05), and induced the cell apoptosis (P < 0.05) by activating caspase-3 and poly (ADP-ribose) polymerase (PARP) proteins (both P < 0.05). Conclusion: AZD5363 can inhibit cell activity and migration, and induce apoptosis of human breast cancer cell line MDA-MB-2 31, thereby exhibiting its anticancer activity.