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目的探讨PI3K/mTOR抑制剂NVP-BEZ235增敏左旋棉酚[(-)-gossypol]杀伤肝癌细胞HepG2的作用及可能机制。方法用NVP-BEZ235、左旋棉酚或二者联合处理HepG2细胞,CCK-8法检测不同处理对细胞增殖的影响,流式细胞术检测不同处理对细胞凋亡的影响,Western blot检测不同处理对细胞中mTOR磷酸化水平以及Mcl-1蛋白水平的影响。结果联合使用NVP-BEZ235和左旋棉酚可显著抑制HepG2细胞增殖,并促进细胞凋亡,其中左旋棉酚可上调HepG2细胞中mTOR磷酸化水平及Mcl-1蛋白水平,导致抵抗发生,NVP-BEZ235能够剂量依赖性抑制mTOR磷酸化(P<0.01),并抑制左旋棉酚对Mcl-1的上调作用。结论 NVP-BEZ235可通过抑制mTOR进而下调Mcl-1来增强左旋棉酚杀伤HepG2细胞的效果。
Objective To investigate the effect and potential mechanism of PI3K / mTOR inhibitor NVP-BEZ235 on HepG2 cells induced by [(-) - gossypol]. Methods HepG2 cells were treated with NVP-BEZ235, L-Gossypol, or both. CCK-8 assay was used to detect the effect of different treatments on cell proliferation. Flow cytometry was used to detect the effect of different treatments on apoptosis. Western blot was used to detect the effect of different treatments The Effect of mTOR Phosphorylation and Mcl-1 Protein Level in Cells. Results The combination of NVP-BEZ235 and L-Gossypol could significantly inhibit HepG2 cell proliferation and promote apoptosis. L-Gossypol could up-regulate mTOR phosphorylation and Mcl-1 protein level in HepG2 cells, resulting in resistance. NVP-BEZ235 It could inhibit mTOR phosphorylation in a dose-dependent manner (P <0.01) and inhibit the up-regulation of Mcl-1 by L-gp. Conclusion NVP-BEZ235 can enhance the effect of L-gossypol on HepG2 cells by inhibiting mTOR and down-regulating Mcl-1.