Inhibition of PI3K/PKB signal pathway improves chemotherapeutic effect on gastric carcinoma cell lines

Aim To observe whether the inhibition of PI3K/PKB signal pathway by LY294002[PI3K pathway inhibitor] could improve the sensitivities of human gastric carcinoma cell line SGC7901 and SGC7901/VCR to anti-cancer drugs.Methods The sensitivities of SGC7901 and SGC7901/VCR to chemotherapeutic drug VCR were detected by MTT.The MDR1 and XIAP mRNA expression levels were evaluated by semi-quantitative RT-PCR,and their protein levels were detected by immunocytochemistry.The PKB and phospho-PKB protein levels were detected by Western blot and the apoptosis ratio was detected by flow cytometry.Results 2×10-5mol·L-1LY294002 enhanced the sensitivities of SGC7901 and SGC7901/VCR cells to VCR(P0.01)significantly,their corresponding IC50decreased from (0.20±0.03) and (8.09±0.6) mg·L-1to (0.05±0.006) and (1.70±0.2) mg·L-1respectively;the mRNA and protein levels of MDR1 and XIAP were reduced by LY294002 obviously.There was obvious reduction in phospho-PKB levels following exposure to LY294002,but it had no effect on PKB levels in either cell line.When treated by LY294002 combined with VCR,the apoptosis ratios of both SGC7901 and SGC7901/VCR cells were much higher than those of VCR alone(P0.01).Conclusion LY294002 could improve the chemotherapeutic sensitivities of human gastric carcinoma cell lines by reducing MDR1 and XIAP expression levels,which might be related to the inhibition of PI3K/PKB signal pathway.