Inhibition of autophagy enhances apoptosis induced by the PI3K/AKT/mTor inhibitor NVP-BEZ235 in renal cell carcinoma cells
Inhibition of autophagy enhances apoptosis induced by the PI3K/AKT/mTor inhibitor NVP-BEZ235 in renal cell carcinoma cells
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DOI：
10.1002/cbf.2917
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发表时间：
2013-07-01
影响因子：
3.6
通讯作者：
Kong, Xiangbo
中科院分区：
文献类型：
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作者：
Li, Hongyan;Jin, Xuefei;Kong, Xiangbo
PI3K/AKT/mTOR通路在大血管肿瘤肾细胞癌(RCC)的发生发展中起关键作用。NVP-BEZ235(NVP)是一种新型的PI3K/mTOR双重抑制剂，具有很好的抗肿瘤作用，为肾癌的治疗提供了新的策略。在本研究中，我们检测了NVP对肾癌细胞系786-0的存活率、细胞凋亡率和自噬的影响。我们还探讨了NVP与自噬抑制剂联合使用导致786-0细胞凋亡增强的假设。结果表明，PI3K/AKT/mTOR通路蛋白p-AKT和p-p70S6K在肾癌组织中高表达。我们还发现，NVP抑制了肾癌细胞的生长，诱导了细胞的凋亡和自噬。NVP与自噬抑制剂联合作用可增强NVP抑制786-0细胞生长和诱导细胞凋亡的作用。本研究提出了一种新的治疗方案，将PI3K/AKT/mTOR途径抑制剂和自噬抑制剂结合起来，促进肾癌细胞的凋亡。版权所有(C)2012 John Wiley&Sons，Ltd.
The PI3K/AKT/mTOR pathway plays a key role in the development of the hypervascular tumor renal cell carcinoma (RCC). NVP-BEZ235 (NVP), a novel dual PI3K/mTOR inhibitor, showed great antitumor benefit and provided a treatment strategy in RCC. In this study, we test the effect of NVP on survival rate, apoptosis and autophagy in the RCC cell line, 786-0. We also explore the hypothesis that NVP, in combination with autophagy inhibitors, leads to apoptosis enhancement in 786-0 cells. The results showed that the PI3K/AKT/mTOR pathway proteins p-AKT and p-P70S6K were highly expressed in RCC tissue. We also showed that NVP inhibited cell growth and induced apoptosis and autophagy in RCC cells. The combination treatment of NVP with autophagy inhibitors enhanced the effect of NVP on suppressing 786-0 growth and induction of apoptosis. This study proposes a novel treatment paradigm where combining PI3K/AKT/mTOR pathway inhibitors and autophagy inhibitors lead to enhanced RCC cell apoptosis. Copyright (c) 2012 John Wiley & Sons, Ltd.