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 expressio

ns of MDR1

Bax and Bcl-2 were evaluated by semi-quantitative PCR with β-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

<

0.01)

while that of Bax was improved significantly (

P

<

0.01). LY294002 improved the growth inhibitory effect of VCR on transplanted gastric carcinoma in nude mice.     Conclusion    Suppressing PI3K/PKB signal pathway by LY294002 reverses the drug resistance of gastric carcinoma cell line SGC7901/VCR. Reduction of MDR1 expression levels

and regulation of apoptosis-related genes

such as Bax and Bcl-2 may play key roles in this progress.