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 p22 phox expression are greatly increased in human prostate cancer tissues, and knockdown of p22 phox by specific small interfering RNA (siRNA) decreased ROS levels in prostate cancer cells. We also showed that stable downregulation of p22 phox in prostate cancer

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... lls 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 p22 phox resulted in inhibition of tumor angiogenesis and tumor growth in nude mice. These findings reveal a new function of p22 phox in tumor angiogenesis and tumor growth, and suggest that p22 phox is a potential novel target for prostate cancer treatment.