Abstract
Objective To investigate the effect of phosphatidylinositol 3 kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor NVP-BEZ235 on apoptosis induced by oxaliplatin in human colon cancer HCT116 cells. Methods Colon cancer HCT116 cells were cultured in vitro with different concentrations of oxaliplatin and/or dual PI3K/mTOR inhibitor NVP-BEZ235. Methyl thiazol tetrazolium (MTT) assay was used to detect the effects of oxaliplatin and/or dual PI3K/mTOR inhibitor NVP-BEZ235 on cell viability of HCT116 cells. Flow cytometry (FCM) was used to detect the effect of oxaliplatin and/or dual PI3K/mTOR inhibitor NVP-BEZ235 on HCT116 cells. Immunofluorescence was used to detect the effect of oxaliplatin and/or dual PI3K/mTOR inhibitor NVP-BEZ235 on the nuclear morphology of HCT116 cells. Western blotting was used to detect the effects of oxaliplatin and/or dual PI3K/mTOR inhibitor NVP-BEZ235 on DNA damage marker gene gamma histone variant H2A histone family member X (γ-H2AX) and apoptosis-related protein expression. Results The results of MTT showed that 2, 4, 8, 16, 32 and 64 μg/ml oxaliplatin inhibited proliferation of HCT116 cells in a dose-dependent manner, and about 16 μg/ml oxaliplatin platinum could decrease 50% HCT116 cells on the growth. The results of flow cytometry revealed that the apoptosis rate of HCT116 cells treated with 4, 16 and 64 μg/ml oxaliplatin was 11%, 36% and 80% respectively (P=0.026). The results of immunofluorescence demonstrated that the combination of oxaliplatin and NVP-BEZ235 obviously induced the apoptosis of HCT116 cells, and the nuclear shrinkage of HCT116 cells. Western blotting indicated that the expression of Cleaved cysteinyl aspartate-specific protease (Caspase)-3 was significantly increased (P=0.026), and the level of γ-H2AX was also up-regulated (P=0.017). Conclusion Dual PI3K/mTOR inhibitor NVP-BEZ235 significantly enhanced the apoptosis of colon cancer cells induced by oxaliplatin and enhanced the DNA damage of colon cancer cells induced by oxaliplatin. Key words: Colon cancer; Dual phosphatidylinositol 3 kinase/mammalian target of rapamycin; Oxaliplatin; Apoptosis; DNA damage
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