Effect of PKB/Akt signal pathway in mifepristone-induced apoptosis in prostate cancer cell line PC-3

Abstract

Objective To investigate the cell apoptosis induced by mifepristone in prostate carcinoma cell line PC-3 and the mechanisms involved. Methods Western blotting analysis was used to detect Akt phosphorylation and associated protein expression in different prostate cancer cell line cells and PC-3 cells treated with mifepristone. Results In PC-3 cells, Akt phosphorylation, that was p-Akt (Thr308) and p-Akt ( Ser473 ) , was significantly higher than the hormone-dependent prostate cancer LNCaP cells, and their expression levels were respectively 0. 27 ±0. 05 and 0. 22 ±0.07, 0.46 ±0.09 and 0. 37 ±0. 10 (P ＜0.05). The p-Akt (Thr308) and p-Akt (Ser473) phosphorylation in PC-3 cells treated with 10 μmol/L mifepristone was significantly decreased. The p-Akt ( Thr308) phosphorylation was particularly marked, its expression was respectively 0. 24 ± 0. 08, 0. 11 ± 0. 03, 0. 05 ± 0. 01 and 0. 01 ± 0. 00 during 4-24 h, and declined rapidly as compared with the p-Akt ( Ser473) phosphorylation which expression levels were respectively 0. 56 ± 0. 17, 0.42 ± 0. 11, 0. 28 ± 0. 09 and 0. 12 ± 0. 05 during 4-24 h. Caspase-9 and caspase-3 were activated into cleavage fragment in the PC-3 cells treated with mifepristone. Conclusion Akt kinase plays an important role in prostate cancer growth, development and hormone-dependent to hormone-independent transformation. The p-Akt ( Thr ) phosphorylation, which plays a dominant role in Akt phosphorylation , is necessary in the course of Akt activation. Mifepristone inhibits prostate cancer PC-3 cell proliferation and induces apoptosis by suppressing the Akt signal transduction pathway and activating caspase. Key words: Prostate carcinoma;  Mifepristone;  Apoptosis;  Akt/PKB signal pathway