Inhibitory effect of LY294002 on gastric cancer
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Abstract
Objective To investigate whether LY294002,a PI3K/Akt signaling pathway specific inhibitor,increases the sensitivity of gastric cancer to anticancer chemotherapeutic agents. Methods Sensitivity of gastric cancer cells to chemotherapeutic agents was evaluated by in vitro MTT assay in the absence or presence of LY294002.Apoptosis of the cells was examined with Annexin V/PI staining.Adriamycin accumulation and retention in cells were determined by flow cytometric analysis.Expression of Bcl-2 protein was detected by Western blotting. Results When SGC7901 cells were treated with chemotherapeutic agents in combination with LY294002,the IC50 values for adriamycin,vincristine or mitomycin significantly decreased with the increasing concentrations of LY294002 compared with those that were treated only with chemotherapeutic agents(P<0.05).Flow cytometric analysis showed that LY294002 significantly increased vincristine-induced apoptosis and adriamycin accumulation and retention(P<0.05).Western blotting showed that the Bcl-2 expression level was significantly lower in LY294002-treated than in untreated SGC7901 cells. Conclusion LY294002 can effectively increase the inhibitory effects of anticancer chemotherapeutic agents on gastric cancer cells.
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