NADPH oxidase subunit p22phox-mediated reactive oxygen species contribute to angiogenesis and tumor growth through AKT and ERK1/2 signaling pathways in prostate cancer |
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Authors: | Qi Li Guang-Bo Fu Ji-Tai Zheng Jun He Xiao-Bing Niu Qiu-Dan Chen Yu Yin Xu Qian Qing Xu Min Wang An-Fang Sun Yongqian Shu Hallgeir Rui Ling-Zhi Liu Bing-Hua Jiang |
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Institution: | 1. State Key Lab of Reproductive Medicine, and Department of Pathology, Cancer Center, Nanjing Medical, Nanjing 210029, China;2. Department of Urology and Pathology, Huai''an First People''s Hospital, Nanjing Medical University, Huai''an 223300, China;3. Department of Pathology, Anhui Medical University, Hefei 230032, China;4. Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China;5. Department of Pathology, Anatomy and Cell Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA |
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Abstract: | Excessive generation of reactive oxygen species (ROS) in cancer cells is associated with cancer development, but the underlying mechanisms and therapeutic significance remain elusive. In this study, we reported that levels of ROS and p22phox expression are greatly increased in human prostate cancer tissues, and knockdown of p22phox by specific small interfering RNA (siRNA) decreased ROS levels in prostate cancer cells. We also showed that stable downregulation of p22phox in prostate cancer cells inhibited cell proliferation and colony formation, which was mediated by AKT and extracellular signal-regulated kinase (ERK)1/2 signaling pathways and their downstream molecules hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF). The NADPH oxidase subunit NOX1 was also elevated in prostate cancer cells, and was involved in activation of AKT/ERK/HIF-1/VEGF pathway and regulation of cell proliferation. Knockdown of p22phox resulted in inhibition of tumor angiogenesis and tumor growth in nude mice. These findings reveal a new function of p22phox in tumor angiogenesis and tumor growth, and suggest that p22phox is a potential novel target for prostate cancer treatment. |
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