Objective: To investigate the correlation between the promoter methylation of TGF-β1 and chemoresistance in epithelial ovarian cancer, and to explore the therapeutic strategy.
Methods: 68 samples of ovarian cancer and 38 normal ovarian tissues were carried out for analysis of the correlation between the promoter methylation of TGF-β1 and chemoresistance in epithelial ovarian cancer. qRT-PCR and Western blotting assay were performed to detect the expression of TGF-β1 and 5- aza-dc. Demethylation reagent was used to detect the effect of methylation on proliferation of cells with resistance to Paclitaxel (PTX).
Results: By comparing the methylation rate between the sensitive cells and resistant cells, we found statistical difference in SKOV3/TR and SKOV cell lines (94.3% versus 42.9%, χ2=64.43, p<0.01), and in A2780/TR and A2780 cell lines (91.4% and 35.2%, χ2=71.38, p<0.01). However, in other cell lines, no statistical difference was seen. The inhibitory rates in SKOV3/TR (0.19 ± 0.01 μm vs. 0.42 ± 0.02 μm, p<0.01) and A2780 (0.012 ± 0.0001 μm vs. 0.33 ± 0.011 μm, p<0.01) cell lines and cell lines treated by different concentrations (0.01, 0.1, 1 and 10 μm), the inhibitory rate was significantly higher than the control group with a statistically significant difference.
Conclusion: Deficiency of TGF-β1 expression caused by promoter methylation can regulate the adhesion, migration, and apoptosis of cells, thereby being involved in the development and progression of ovarian cancer. With the reversible feature of methylation, it can serve as a therapeutic target in the comprehensive treatment of ovarian cancer.Author(s): Gui-ying Chen, Feng-di Hu, Jiang-qiong Han, Li-hua Yang