NADPH oxidase subunit p22(phox)-mediated reactive oxygen species contribute to angiogenesis and tumor growth through AKT and ERK1/2 signaling pathways in prostate cancer. Biochim Biophys Acta 2013 Dec;1833(12):3375-3385
Date
10/12/2013Pubmed ID
24113386DOI
10.1016/j.bbamcr.2013.09.018Scopus ID
2-s2.0-84886843534 (requires institutional sign-in at Scopus site) 38 CitationsAbstract
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 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 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.
Author List
Li Q, Fu GB, Zheng JT, He J, Niu XB, Chen QD, Yin Y, Qian X, Xu Q, Wang M, Sun AF, Shu Y, Rui H, Liu LZ, Jiang BHMESH terms used to index this publication - Major topics in bold
AnimalsCell Line, Tumor
Cell Proliferation
Gene Knockdown Techniques
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
MAP Kinase Signaling System
Male
Mice
Mice, Nude
NADPH Oxidases
Neovascularization, Pathologic
Prostatic Neoplasms
Proto-Oncogene Proteins c-akt
Reactive Oxygen Species
Tumor Stem Cell Assay
Vascular Endothelial Growth Factor A