Suppressing PI3K/PKB signal pathway to reverse drug resistance of gastric carcinoma cell line SGC7901/VCR:efficiency and mechanism / 第三军医大学学报

ABSTRACT

Objective To investigate the reversing effects on drug resistance of gastric carcinoma by suppressing PI3K/PKB signal pathway,and explore its implicated mechanism.Methods MTT assay was used to test the inhibitory effects of VCR alone or VCR in combination with PI3K/PKB inhibitor,LY294002 on SGC7901/VCR cells.The SGC7901 treated with or without LY294002 served as control.The protein levels of PKB and phospho-PKB in the above VCR cells were determined by Western blot analysis.The mRNA expressions of MDR1,Bax and Bcl-2 were evaluated by semi-quantitative PCR with ?-actin as the inner control.The apoptosis was detected by flow cytometry.Tumor volume on the tumor-bearing mice transplanted by SGC7901/VCR cells or cells treated by VCR,LY294002 and their combination respectively was measure for the in vivo effect of LY294002.Results LY294002 enhanced the sensitivities of SGC7901/VCR cells to VCR significantly,and promoted the apoptosis rate induced by VCR prominently,with their corresponding drug resistant index decreasing from 40.45 to 8.50.The protein level of phospho-PKB was reduced,and the mRNA expression levels of MDR1 and Bcl-2 were inhibited(P