Synergistic anti-tumor effects of a novel phosphatidyl inositol-3 kinase/mammalian target of rapamycin dual inhibitor BGT226 and gefitinib in non-small cell lung cancer cell lines.

Epidermal growth factor receptor (EGFR) and PI3K/mTOR pathway are drug targets for non-small cell lung cancer (NSCLC). Herein, we investigated anti-tumor effects of the combination of BGT226, a novel PI3K/mTOR dual inhibitor, and gefitinib on NSCLC cell lines which are high sensitive to gefitinib. The combination of BGT226 and gefitinib exhibited supra-additive growth inhibitory effects in PC-9 and HCC827 cells. Apoptotic induction and the inhibition of PI3K/mTOR signaling were enhanced by the combination. Significant tumor growth suppression was observed in xenograft model by the combination. These results suggest that the combination is effective in EGFR inhibitor-sensitive NSCLC therapy.