Effect of activation of protein kinase B and Caspase-9 signal transduction pathway of human gastric cancer cells on the cell chemosensitivity to etoposide / 中华消化杂志

ABSTRACT

Objective To investigate the effect of activation of protein kinase B(PKB) and Caspase-9 signal transduction pathway of human gastric cancer cells on the cell growth and chemosensitivity to etoposide.Methods The gastric cancer cells SGC7901 were treated with etoposide or etoposide plus PKB inhibitor Wortmannin at different time.The growth rates of gastric cancer cells SGC7901 and their sensitivity to etoposide were examined by 3-(4,5-dimethylthiazol-2,1)-2,5 diphanytetrazolium(bromide) assay.Apoptosis of gastric cancer cells was(detected) by flow cytometry.PKB activity was measured by(immunoprecipitation.) Caspase-3 expression and Caspase-9 activity were determined by Western bolt analysis.Results Etoposide induced apoptosis of SGC7901 cells and inhibited its survival effectively,which was much(weaker) 12 h after treatment.PKB(activity) became higher gradually,and Caspase-3 expression,Caspase-9(activity) significantly reduced at 12 h treated with etoposide.(Conversely),after pretreated with Wortmannin,PKB activity remarkably(reduced,) and Caspase-3(expression),Caspase-9 activity markedly increased.(Wortmannin) suppressed growth and potentiated (apoptosis) caused by etoposide.Potentiation of apoptosis by Wortmannin(correlated) with etoposide-induced PKB and Caspase-9 phosphorylation.Conclusions PKB and Caspase-9 signal transduction pathway promotes(human) gastric cancer cells survival and resistance to(chemotherapy.) PKB inhibitor can enhance sensitivity of gastric cancer cells to chemotherapy.