Combined Application of Phosphoinositide 3-Kinase and Mammalian Target of Rapamycin Inhibitors Suppresses Cell Growth and Promotes Apoptosis in Human Lung Cancer Cell Lines

Abstract

PI3K/Akt/mTOR would be an important intracellular signal pathway which has found to be over-activated in neoplasia. Here, the combination effect of LY294002 (PI3K inhibitor) and rapamycine (mTOR inhibitor) has evaluated in different human lung cancer cell lines. MTT assay has used to assess the viability of Calu-6, SK-MES-1 and A549 cancer cells. The levels of biochemical markers of apoptosis (activated caspase-3) and cell proliferation (c-Myc and cyclin D1) have evaluated by immunoblotting. The data has shown that blockade of PI3K/Akt cascade with LY294002 (0.1-100 µM) resulted in growth inhibition with IC50 ranging from 7 to 35 µM.LY294002 plus rapamycin (10 nM) significantly enhanced the growth inhibition rate and elevated cleaved caspase-3 in A549 and SK-MES-1 cells. Moreover, such combination therapy had a potent decreasing effect on c-Myc and cyclin D1 protein levels. Taken together, combined inhibition of PI3K/Akt/mTOR signaling has represented a promising treatment strategy for lung cancer but the effectiveness of such combination therapy has been depending on the cancer cell types.