NVP-BEZ235增敏左旋棉酚杀伤肝癌HepG2细胞的作用  

Effect of NVP-BEZ235 on sensitization of HepG2 cells to(-)-gossypol

作　　者：王滨[1] 倪振洪[1] 丁雯[1] 秦利燕[1] 连继勤[1] 何凤田[1] 

机构地区：[1]第三军医大学基础医学部生物化学与分子生物学教研室,重庆400038

出　　处：《第三军医大学学报》2013年第19期2024-2027,共4页Journal of Third Military Medical University

基　　金：重庆市自然科学基金(CSTC2011BB5030)~~

摘　　要：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 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 roTOR were detected by Western blotting. Results Compared to （-）-gossypo] 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 close-dependent manner and attenuated （-） -gossypol-induced Mcl-I accumu- lation. Conclusion NVP-BEZ235 sensitized HepG2 cells to （-）-gossypol partly by inhibiting roTOR phos- phoralation and down-regulating Mcl-1.

关 键 词：左旋棉酚 NVP-BEZ235 MTOR 肝细胞癌 

分 类 号：R73-361[医药卫生—肿瘤] R979.1[医药卫生—临床医学]