[1]王滨,倪振洪,丁雯,等.NVP-BEZ235增敏左旋棉酚杀伤肝癌HepG2细胞的作用[J].第三军医大学学报,2013,35(19):2024-2027.
 Wang Bin,Ni Zhenhong,Ding Wen,et al.Effect of NVP-BEZ235 on sensitization of HepG2 cells to (-)-gossypol[J].J Third Mil Med Univ,2013,35(19):2024-2027.
点击复制

NVP-BEZ235增敏左旋棉酚杀伤肝癌HepG2细胞的作用(/HTML )
分享到:

《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
35卷
期数:
2013年第19期
页码:
2024-2027
栏目:
论著
出版日期:
2013-10-15

文章信息/Info

Title:
Effect of NVP-BEZ235 on sensitization of HepG2 cells to (-)-gossypol
作者:
王滨倪振洪丁雯秦利燕连继勤何凤田
第三军医大学基础医学部生物化学与分子生物学教研室
Author(s):
Wang Bin Ni Zhenhong Ding Wen Qin Liyan Lian Jiqin He Fengtian
Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing, 400038, China
关键词:
左旋棉酚NVP-BEZ235mTOR肝细胞癌
Keywords:
(-)-gossypol NVP-BEZ235 mTOR hepatocellular carcinoma
分类号:
R73-361; R735.7; R979.1
文献标志码:
A
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。
Abstract:
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.

参考文献/References:

王滨,倪振洪,丁雯,等. NVP-BEZ235增敏左旋棉酚杀伤肝癌HepG2细胞的作用[J].第三军医大学学报,2013,35(19):2024-2027.

相似文献/References:

[1]丁雯,倪振洪,程攀科,等.左旋棉酚通过细胞自噬下调Namalwa细胞中B淋巴细胞刺激因子的表达[J].第三军医大学学报,2012,34(16):1613.
 Ding Wen,Ni Zhenhong,Cheng Panke,et al.Mechanism of (-)-gossypol down-regulating B lymphocyte stimulator expression in Namalwa cells via autophagy[J].J Third Mil Med Univ,2012,34(19):1613.
[2]倪振洪,王滨,丁雯,等.左旋棉酚通过ERK通路诱导Daudi细胞发生自噬及意义[J].第三军医大学学报,2012,34(23):2384.
 Ni Zhenhong,Wang Bin,Ding Wen,et al.(-)-gossypol induces autophagy in Daudi cells through ERK signal pathway[J].J Third Mil Med Univ,2012,34(19):2384.

更新日期/Last Update: 2013-09-30