Atorvastatin reduces vascular endothelial growth factor (VEGF) expression in human non-small cell lung carcinomas (NSCLCs) via inhibition of reactive oxygen species (ROS) production
Atorvastatin reduces vascular endothelial growth factor (VEGF) expression in human non-small cell lung carcinomas (NSCLCs) via inhibition of reactive oxygen species (ROS) production
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阿托伐他汀通过抑制活性氧 (ROS) 的产生来降低人非小细胞肺癌 (NSCLC) 中血管内皮生长因子 (VEGF) 的表达
DOI：
10.1016/j.molonc.2011.11.003
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发表时间：
2012-02-01
影响因子：
6.6
通讯作者：
Li, Xuejun
中科院分区：
文献类型：
--
作者：
Chen, Jie;Liu, Bing;Li, Xuejun
非小细胞肺癌（NSCLC）的高转移潜能与血管内皮生长因子（VEGF）的高表达以及由此产生的肿瘤血管生成密切相关。然而，在NSCLC治疗中没有针对VEGF表达的有效策略。这项研究表明，来自线粒体和NADPH氧化酶的活性氧（ROS）水平升高是NSCLC细胞中VEGF表达所必需的。阿托伐他汀给药可通过抑制ROS的产生，在体内外显著抑制VEGF的表达。阿托伐他汀通过抑制Rac 1/NADPH氧化酶活性抑制ROS生成。具体而言，阿托伐他汀可上调谷胱甘肽过氧化物酶（GPx）和过氧化氢酶的活性，这两种酶分别负责清除线粒体和过氧化物酶体中的过氧化氢（H2 O2）。因此，通过同时抑制Rac 1/NADPH氧化酶活性和上调GPx和过氧化氢酶活性来抑制ROS产生，对阿托伐他汀降低NSCLC中VEGF表达起关键作用。阿托伐他汀可能是NSCLC治疗中抑制VEGF表达和血管生成的潜在替代药物。(C)2011年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
The high metastatic potential of non-small cell lung cancers (NSCLCs) is closely correlated with the elevated expression of vascular endothelial growth factor (VEGF) and resultant tumor angiogenesis. However, no effective strategies against VEGF expression have been available in NSCLCs therapy. This study demonstrated that elevated reactive oxygen species (ROS) levels derived from both mitochondria and NADPH oxidase were required for VEGF expression in NSCLC cells. Atorvastatin administration could significantly inhibit VEGF expression both in vitro and in vivo via inhibition of ROS production. Atorvastatin inhibited ROS generation partly through suppression of Rac1/NADPH oxidase activity. Specifically, atorvastatin could upregulate the activity of glutathione peroxidase (GPx) and catalase, which are responsible for elimination of hydrogen peroxide (H2O2) in the mitochondria and peroxisomes, respectively. Thus, inhibition of ROS production by concomitant suppression of Rac1/NADPH oxidase activity and upregulation of the activity of GPx and catalase contributes critically to atorvastatin-reduced VEGF expression in NSCLCs. Atorvastatin may be a potential alternative against VEGF expression and angiogenesis in NSCLCs therapy. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.