TGFBI promoter hypermethylation correlating with paclitaxel chemoresistance in ovarian cancer

The purpose of this study is to determine the methylation status of transforming growth factor-beta-inducible gene-h3 (tgfbi) and its correlation with paclitaxel chemoresistance in ovarian cancer. the methylation status of tgfbi was examined in ovarian cancer and control groups by methylation-specific pcr (msp) and bisulfite sequencing pcr (bsp). the tgfbi expression and cell viability were compared by quantitative real-time pcr,western blotting and mtt assay before and after demethylating agent 5-aza-2'-deoxycytidine (5-aza-dc) treatment in 6 cell lines (skov3,skov3/tr,skov3/ddp,a2780,2780/tr,ovcar8). in our results,tgfbi methylation was detected in 29/40 (72.5%) of ovarian cancer and 1/10 (10%) of benign ovarian tumors. no methylation was detected in normal ovarian tissues (p < 0.001). no statistical correlation between runx3 methylation and clinicopathological characteristics was observed. a significant correlation between tgfbi methylation and loss of tgfbi mrna expression was found (p < 0.001). the methylation level of tgfbi was significantly higher in paclitaxel resistant cell lines (skov3/tr and 2780/tr) than that in the sensitive pairs (p < 0.001). after 5-aza-dc treatment,the relative expression of tgfbi mrna and protein increased significantly in skov3/tr and a2780/tr cells. however,no statistical differences of relative tgfbi mrna expression and protein were found in other cells (all p > 0.05),which showed that re-expression of tgfbi could reverse paclitaxel chemoresistance. our results show that tgfbi is frequently methylated and associated with paclitaxel-resistance in ovarian cancer. tgfbi might be a potential therapeutic target for the enhancement of responses to chemotherapy in ovarian cancer patients. © 2012 wang et al; licensee biomed central ltd.