Objective      To determine the effect and associated mechanisms of PI3K/mTOR inhibitor NVP-BEZ235 on the sensitization of HepG2 cells to Bcl-2 inhibitor

(-)-gossypol.       Methods      HepG2 cells were treated with NVP-BEZ235

(-)-gossypol or combined these 2 agents. The anti-proliferation effects of different treatments were detected by CCK-8 assay and cell apoptosis was detected by flow cytometry. Protein level of myeloid cell leukemia-1 (Mcl-1) and phosphoralation levels of mTOR were detected by Western blotting.       Results      Compared to (-)-gossypol alone

the combination of NVP-BEZ235 and (-)-gossypol significantly inhibited the proliferation and induced the apoptosis in HepG2 cells. (-)-gossypol upregulated the protein expression of Mcl-1 and the phosphoralation of mTOR in HepG2 cells

while NVP-BEZ235 inhibited the phosphoralation levels of mTOR in dose-dependent manner and attenuated (-)-gossypol-induced Mcl-1 accumulation.       Conclusion      NVP-BEZ235 sensitized HepG2 cells to (-)-gossypol partly by inhibiting mTOR phosphoralation and down-regulating Mcl-1.