Evaluating of 5-azacytidine and trichistatin a effect on mir-152 expression in cisplatin resistance a2780 ovarian cancer cell line

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic cancers in women.Cisplatin is the front-line chemotherapeutic agent for ovarian cancer treatment. But the development ofresistance to cisplatin is the main clinical obstacle to successful treatment of ovarian cancer. Epigenetic aberrations are one underlying mechanism of acquired Cisplatin resistance. MicroRNAs are small non- coding RNAs that regulate gene expression at the post-transcriptional level. miR-152 expression is frequently downregulated in many types of cancers including cancer of the ovary. It is observed thatthe overexpression of miR-152 can return Cisplatin sensitivity by targeting DNMT1. In this study, the effect of 5-azacytidine and Trichostatin A was investigated on miR-152 expression in A2780CP ovariancancer cell line.Optimal concentration of 5-azacytidine and Trichostatin A was examined by MTT assay. After that A2780CP cells were treated with these two epidrugs alone or in combination, Real-time PCR was performed to assess the relative expression of miR-152 and DNMT1 in comparison with control group.There was no significant change in expression of miR-152 after treatment with 5-azacytidine and Trichostatin A separately, but co-treatment with both two epidrugs significantly increased miR-152 expression in A2780CP cells. Co-treatment of A2780CP cells with 5-azacytidine and Trichostatin Acould be resulted in re-expression of miR-152 in A2780CP cells. These findings suggest that pretreatment using histone deacetylase inhibitors and DNA methyl transferases in combination with Cisplatin may be beneficial for reducing cancer relapse in patients with advanced ovarian cancer

کلیدواژه ها:

Ovarian Cancer ، Cell and Cancer ، Cancer Treatment and Management ، Drugs and Cancer ، Chemotherapy