Inhibition of p22 phox Suppresses Epithelial Ovarian Cancer Cell Proliferation and Tumorigenesis.

The aim of this study was to investigate the biological role and molecular mechanism of p22 ^phox in epithelial ovarian cancer. Immunohistochemistry was employed to determine the p22 ^phox expression level in epithelial ovarian cancer tissues. The effects of p22 ^phox on epithelial ovarian cancer cell proliferation, tumorigenesis, and chemosensitivity were evaluated by CCK-8, EdU assay, colony formation and apoptosis assays in vitro and by mouse experiments in vivo. Immunoprecipitation analyses were utilized to explore the potential mechanisms of p22 ^phox mediated downstream signaling, and RT-PCR and western blot were used to confirm the relevance. P22 ^phox expression could be detected in epithelial ovarian cancer tissues and normal fallopian epithelial cells. Silencing p22 ^phox suppressed epithelial ovarian cancer cell proliferation and colony formation capacity in vitro , and inhibited the tumor growth in nude mice bearing the A2780 xenograft in vivo . Mechanistic investigations showed that p22 ^phox regulated proteasome ubiquitination and subsequent proteasome-dependent degradation of p53 in A2780 and U87 cells in vitro . Furthermore, knockdown of p22 ^phox significantly increased the chemosensitivity of A2780 cells to cisplatin or paclitaxel. These results suggested that p22 ^phox as a pivotal oncogene during epithelial ovarian cancer carcinogenesis and p22 ^phox inhibition might be a potential therapeutic strategy for epithelial ovarian cancer.
Competing Interests: Competing Interests: The authors have declared that no competing interest exists.
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