Role of cell division cycle associated 2 in ovarian cancer: Effects on tumor progression and cisplatin resistance.

OBJECTIVE: Ovarian cancer is a disease that seriously endangers the health and life safety of women. At present, no effective preventive and therapeutic measures are available. This study probed the impact of cell division cycle-associated 2 (CDCA2) on ovarian cancer development and cisplatin sensitivity, which provides a new research direction for the study of ovarian cancer. MATERIAL AND METHODS: The protein expression level of CDCA2 was tested by Western blot assay. Cell proliferation was evaluated by cell cloning formation assay and Celigo cell counting. Cell invasion and migration were assessed by Transwell assay. An experiment for nude mouse tumor formation was conducted to analyze the influence of CDCA2 knockdown on tumor growth in vivo. We treated CDCA2 knockdown cells with gradient cisplatin and measured cell viability using the cell counting kit-8 assay. Apoptosis and DNA damage induced by CDCA2 knockdown were investigated by flow cytometry and histone family member X (H2AX) phosphorylated on Ser 139 (γ-H2AX) immunofluorescence, respectively. RESULTS: CDCA2 expression was knocked down in A2780 and SKOV3 cells. After CDCA2 knockdown, cell proliferation, migration, and invasion ability decreased significantly, and tumor growth in vivo was also limited (P < 0.01). The phosphorylation levels of protein kinase B (AKT) and mechanistic target of rapamycin (mTOR) were reduced by CDCA2 knockdown (P < 0.01), but the effect was reversed by the AKT activator SC-79 (P < 0.01). Knockdown of CDCA2 increased the cisplatin sensitivity of ovarian cancer cells by enhancing apoptosis and DNA damage (P < 0.01). CONCLUSION: CDCA2 knockdown inhibited the development of ovarian cancer through the AKT/mTOR pathway and enhanced cisplatin sensitivity. CDCA2 is a potential target to reverse cisplatin resistance in ovarian cancer. It can also be used as a new research direction for the development of ovarian cancer therapy.