期刊
MOLECULAR ONCOLOGY
卷 6, 期 1, 页码 62-72出版社
WILEY
DOI: 10.1016/j.molonc.2011.11.003
关键词
Non-small cell lung cancers; NSCLCS; Vascular endothelial growth factor; VEGF; Reactive oxygen species; ROS; NADPH oxidase; Atorvastatin
类别
资金
- National Natural Science Foundation of China [81020108031, 30572202, 30973558, 30772571, 30901815, 30901803]
- Ministry of Science and Technology in China [2009ZX05103-144]
- Ministry of Education of China [B07001]
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.
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