Effect of Vav3 gene inhibition on inhibitor of apoptosis proteins and multidrug resistance in gastric cancer cells

Abstract

Objective To explore the role of Vav3 gene in multidrug resistance(MDR)of gastric cancer and the related mechanism.Methods QRT-PCR was used to examine the expressions of Vav3 gene in gastric cancer tissues,tumor-adjacent tissues,human gastric cancer cell line SGC7901,and gastric epithelial cell line GES-1.Then Vav3-siRNA was synthesized and tansfected into SGC7901 cells. MTT assay was then used to determine the inhibition rates of tumor cells exposed to chemotherapeutic agents(5-FU,L-OHP)before and after Vav3-siRNA transfection.Real-time RT-PCR and Western blotting analysis were used to observe the expressions of inhibitor of apoptosis proteins(IAPs):xIAP,Survivin,and Livin;meanwhile,the expression and activity of Caspase-3and Caspase-8 were also determined.Results Vav3 was over-expressed in gastric cancer tissues and gastric cell line compared with those in tumor-adjacent tissues and gastric epithelial cell line GES-1(P0.05).Expression of Vav3 was significantly inhibited by Vav3-siRNA(P0.01).Inhibition rates of tumor cells exposed to 5-FU and L-OHP were significantly increased 48 hafter Vav3-siRNA tansfection(P0.05).The expressions of xIAP and Survivin were significantly decreased in cancer cells after Vav3-siRNA tansfection(both P0.05),and no notable change was found for Livin expression;also the expression and activity of Caspase-3and Caspase-8protein were significantly increased after Vav3-siRNA tansfection in SGC7901cells(all P0.05).Conclusion Vav3 can participate in MDR of gastric cancer by regulating apoptotic pathways,and inhibition of Vav3 can help reverse MDR of gastric cancer cells by regulating some IAPs.