Affiliations: [a] Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China | [b] Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
Correspondence:
[*]
Corresponding author: Lin Guo, Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, No.270, Dong'An Road, Xuhui District, Shanghai 200032, China. Tel.: +86 21 6417 5590 82204; Fax: +86 21 6417 5590 82204; E-mail:Guolin500@hotmail.com
Note: [1] These authors contributed equally to this work.
Abstract: 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
APE1 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 APE1 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.
