APE1 overexpression promotes the progression of ovarian cancer and serves as a potential therapeutic target

作者：Wen, Xuemei; Lu, Renquan; Xie, Suhong; Zheng, Hui; Wang, Hongling; Wang, Yanchun; Sun, Jiajun; Gao, Xiang; Guo, Lin^*

来源：Cancer Biomarkers, 2016, 17(3): 313-322.

DOI：10.3233/CBM-160643

• Apurinic/apyrimidinic endonuclease 1
• ovarian cancer
• proliferation
• apoptosis

BACKGROUND: Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional enzyme that is involved in DNA repair and the redox regulation of transcription factors. Blocking these functions leads to cell-growth inhibition, apoptosis and other effects. Previous studies have demonstrated that high expression levels of the APE1 protein are associated with the progression and chemoresistance of cancers. We hypothesized that APEI silencing in ovarian cancer cells might have anticancer effects mediated by cell-growth inhibition and an increase in drug-sensitivity.
OBJECTIVE: In this study, we explored the consequences of APE1 silencing in ovarian cancer cells.
METHODS: Immunohistochemistry (IHC) was used to detect the APE1 protein levels in tissue samples from twelve ovarian cancer (OC) patients and eleven non-OC patients. APE1 knockdown was achieved via the stable transfection of SKOV3 and A2780 cells with a construct encoding a short hairpin DNA directed against the APE1 gene. Then, cell proliferation, colony formation, cell cycle and apoptosis assays were performed to reveal the consequences of APE1 silencing in ovarian cancer cells. Additionally, the SKOV3 and A2780 cells were subjected to the treatment with camptothecin (CPT) and ultraviolet rays (UV) to assess the possible link between the APE1 protein and drug-resistance.
RESULTS: Our results revealed that the APE1 protein was overexpressed in OC tissues. APE1 knockdown in A2780 and SKOV3 cells reduced cell proliferation, arrested cell cycle progression, repressed colony formation and weakly promoted cell apoptosis through the BAX and BCL-2 apoptotic pathways. Additionally, the down-regulation of APEI significantly enhanced the sensitivity of ovarian cancer cells to the CPT/UV treatment.
CONCLUSION: Our study suggested that the APE1 protein is important for the proliferation and growth of ovarian cancer cells. APE1 silencing might enhance drug-sensitivity, and thus APE1 might serve as a novel anti-OC therapeutic target.

• 出版日期2016
• 单位复旦大学