Silencing of Apurinic/Apyrimidinic Endonuclease 1 Inhibits the Growth and Migration in Ovarian Cancer Cell via Activator-Protein-1 Signaling.

BACKGROUND: We hypothesized that apurinic/apyrimidinic endonuclease 1 (APE1) may regulate cell activity via activator protein 1 (AP-1) signaling pathway through its redox function in the development of ovarian cancer.

METHODS: Ovarian cancer and paired paracarcinoma tissues were collected for determining APE1 expression with immunohistochemistry. Cell transfection was performed to silence APE1. For mRNA and protein expressions of genes after silencing, real-time reverse transcription polymerase chain reaction and Western blot assay were conducted. Transwell cell proliferation experiment and clone formation assay were conducted for cell proliferation; Transwell cell migration and cell invasion assays were conducted for cell migration and invasion.

RESULTS: Most cancer tissues had APE1 cytoplasmic expression and a few had nuclear/cytoplasmic expression while few had only nuclear expression. A significantly higher APE1 expression was identified in cancer tissues than in paracarcinoma tissues and it was correlated with the clinicopathologic features. SKOV3 was used for cell experiments. After silencing of APE1, both mRNA and protein expressions of APE1 and AP-1 signaling-related genes were downregulated, and the cell activity in proliferation, migration and invasion was remarkably suppressed.

CONCLUSION: Overexpressed APE1 promotes ovarian cancer growth and metastasis. Downregulated APE1 could suppress cell activity via AP-1 pathway, suggesting that APE1 gene may be a potential therapeutic target for ovarian cancer.