摘要
Objective:Apurinic/apyrimidinic endonuclease 1(APE1) has been recognized as a promising anticancer target in several malignancies,and its selective inhibitors such as APX3330 has been advanced in research recently.However,the anticancer effect of APE1 against ovarian cancer(OC) has not been well investigated.In this study,we explored the biological function of APE1 in ovarian cancer cells and its anticancer effect as a therapeutic target in OC.Methods:Immunohistochemistry(IHC) was used to detect the APE1 protein levels in tissue samples from 12 OC patients and 11 Non-OC patients.Knockdown of APE1 expression was achieved by 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-associated assays were performed to reveal the biological function of APE1 in ovarian cancer cells.In addition,SKOV3 and A2780 cells were treated with Camptothecin(CPT) and Ultraviolet Rays(UV) to assess the link between APE1 and chemoresistance.Results:Our results showed that APE1 was overexpressed in OC tissues.Knockdown of APE1 in A2780 and SKOV3 reduced cell proliferation,arrested cell cycle progression,repressed colony formation and slightly promoted cell apoptosis through BAX and Bcl-2 apoptosis pathways.In addition,down-regulation of APE1 significantly enhanced the sensitivity of ovarian cancer cells to CPT and UV.Conclusion:Our study suggested that APE1 may be essential for the growth of ovarian cancer cells,implicating a potential new therapeutic target for OC.
Objective:Apurinic/apyrimidinic endonuclease 1(APE1) has been recognized as a promising anticancer target in several malignancies,and its selective inhibitors such as APX3330 has been advanced in research recently.However,the anticancer effect of APE1 against ovarian cancer(OC) has not been well investigated.In this study,we explored the biological function of APE1 in ovarian cancer cells and its anticancer effect as a therapeutic target in OC.Methods:Immunohistochemistry(IHC) was used to detect the APE1 protein levels in tissue samples from 12 OC patients and 11 Non-OC patients.Knockdown of APE1 expression was achieved by 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-associated assays were performed to reveal the biological function of APE1 in ovarian cancer cells.In addition,SKOV3 and A2780 cells were treated with Camptothecin(CPT) and Ultraviolet Rays(UV) to assess the link between APE1 and chemoresistance.Results:Our results showed that APE1 was overexpressed in OC tissues.Knockdown of APE1 in A2780 and SKOV3 reduced cell proliferation,arrested cell cycle progression,repressed colony formation and slightly promoted cell apoptosis through BAX and Bcl-2 apoptosis pathways.In addition,down-regulation of APE1 significantly enhanced the sensitivity of ovarian cancer cells to CPT and UV.Conclusion:Our study suggested that APE1 may be essential for the growth of ovarian cancer cells,implicating a potential new therapeutic target for OC.
引文