Combination of cecropinXJ and LY294002 induces synergistic cytotoxicity, and apoptosis in human gastric cancer cells via inhibition of the PI3K/Akt signaling pathway

摘要

The aim of the present study was to investigate the cytotoxic and apoptotic effects of cecropinXJ against human gastric cancer BGC823 cells, either alone, or in combination with a specific phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002. Cell viability and the apoptosis rate were measured using flow cytometry with Annexin-V staining. Additionally, the expression levels of several RAC-alpha serine/threonine kinase (Akt) phosphorylation-associated proteins and apoptosis-regulating proteins were evaluated by western blot analysis. It was observed that the combination of cecropinXJ and LY294002 resulted in significant synergistic cytotoxic and apoptosis effects, as compared with any single agent alone, in a dose-dependent manner. Corresponding to enhanced apoptosis, the expression levels of certain apoptosis-regulating proteins were changed, the most notable being the upregulation of caspase-3, B-cell lymphoma-2 (Bcl-2)-associated death promotor, Bcl-2 homologous antagonist killer, Bcl-2 interacting killer, Bcl-2-like protein 11, Bcl-2-like protein 4 and cytochrome c, and the downregulation of phosphorylated-Bad and Bcl-2 proteins. The present study provided a novel therapeutic regimen for the use of the cecropinXJ in combination with LY294002 for the treatment of gastric cancer.