Resensitization of cisplatin-resistant ovarian cancer cells by DNA demethylating agents

Abstract

Ovarian cancer is one of the most lethal gynecologic malignancies. Since most ovarian cancer cases were diagnosed in the late stages, drug resistance and metastasis are the major impediment in successful treatment of ovarian cancer. It is now commonly accepted that aberrations in DNA methylation may play an important role in tumorigenesis and drug resistance. It was also suggested that DNA demethylating agents would be promising chemotherapies to reverse drug-resistant phenotypes in previous studies. To investigate the effect of DNA demethylating agents in resensitization, cytotoxicity assays and several apoptosis assays were performed using R5, the cisplatin-resistant ovarian cancer cell line which had been established in vitro. Pretreatment of 5-aza-dC or zebularine was shown to cause decrease of 50% effective concentration of cisplatin in dose-dependent manner. Although there were no clear evidences of cisplatin-induced apoptosis in both R0 and R5 cells, it can be suggested that combined treatment of 5-aza-dC or zebularine with conventional chemotherapies is worth to develop as a promising strategy for overcoming drug-resistant tumors.