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

Abstract

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.

Aberrant serum and tissue levels of Beclin1 and mechanistic target of rapamycin (mTOR) proteins in epithelial ovarian cancer

“…Ovarian cancer is a common gynecological cancer with different cell origins. [1][2][3] In particular, epithelial ovarian cancer comprises approximately 80% to 90% of all ovarian cancer cases, with a 5-year survival rate of approximately 10% to 20%. [4] Thus, further identification and evaluation of biomarkers might facilitate early diagnosis and predict the prognosis and treatment outcomes for epithelial ovarian cancer patients.…”