The role of methyltransferase inhibitor 5-Aza-dC in regulation of the expression of FANCF gene in the treatment of ovarian cancer / 肿瘤

ABSTRACT

Objective: To investigate the effect of methyltransferase inhibitor 5-Aza-dC (5-aza-2'- deoxycytidine) on the expression of FANCF (Fanconi anemia complementation group F) gene in ovarian cancer OVCAR3 cells, and examine its effect on the sensitivity to chemotherapeutic drug paclitaxel in ovarian cancer in vitro , and to explore the antitumor effect of 5-Aza-dC as a new target for treatment of ovarian cancer. Methods: The ovarian cancer OVCAR3 cells (methylated FANCF gene) and A2780 cells (unmethylated FANCF gene) were treated with 5-Aza-dC. The methylation status of FANCF gene and the expression levels of FANCF mRNA and protein in OVCAR3 and A2780 cells before and after the treatment with 5-Aza-dC were detected by MSP (methylation-specific PCR), RT-PCR and Western blotting, respectively. The proliferation rate of these ovarian cancer cells was detected by MTT method, and the apoptosis rate of these cells treated with paclitaxel was measured by FCM (flow cytometry). The xenografts were induced in nude mice transplanted with OVCAR3 cells or A2780 cells. The effect of 5-Aza-dC on the growth of the xenografts in nude mice was observed. The expression of FANCF protein in the xenografts was detected by immunohistochemistry. Results: DNA promoter methylation disappears in OVCAR3 cells after treatment with 5-Aza-dC, and the expression levels of FANCF mRNA and protein were increased in vitro . The growth of OVCAR3 cells was also slowed down. The volume and the weight of OVCAR3 ovarian cancer xenografts treated with 5-Aza-dC were both significantly decreased as compared with those of the untreated xenografts in nude mice; the expression of FANCF protein in the xenografts was increased after treatment with 5-Aza-dC. These changes were not observed in A2780 ovarian cancer xenografts in nude mice. Conclusion: The methyltransferase inhibitor 5-Aza-dC may become a potential therapeutic drug in the treatment of ovarian cancer through inhibiting the proliferation of ovarian cancer cells, but it can also increase the risk of resistance to paclitaxel. © 2012 by Tumor.