Effect of MiR-449c-5p on the sensitivity of ovarian cancer cells to paclitaxel and its mechanism
Objective To explore the effects of miR-449c-5p on the paclitaxel(PTX)sensitivity of PTX-resistant ovarian cancer cells and the potential regulatory mechanism.Methods MiR-449c-5p expression was analyzed by qRT-PCR,and ABCC1 protein expression was detected by western blotting assay.PTX-resistant ovarian cancer cells including A2780/PTX and SKOV3/PTX were transfected with miR-449c-5p,miR-NC,ABCC1 overexpression vector and pcDNA 3.1(+)vector,and then cell phenotypic changes were analyzed by CCK-8 assay and transwell assay.Dual-luciferase reporter assay was used to identify the association between miR-449c-5p and ABCC1.The effect of combination treatment of miR-449c-5p and PTX on tumor growth was analyzed in vivo by a xenograft mouse model assay.Results Compared with HOSEPiC cells,miR-449c-5p expression was lower in A2780 and SKOV3 cells(P＜0.05),and was the lowest in A2780/PTX and SKOV3/PTX cells(P＜0.05).MiR-449c-5p interacted with ABCC1 in A2780/PTX and SKOV3/PTX cells.Compared with the miR-NC transfection group,the miR-449c-5p transfection group showed reduced IC50 value of PTX and the decreased number of invasive cells(P＜0.05).Compared with the miR-449c-5p and pcDNA co-transfection group,the IC50 value of PTX and the number of invasive cells in the miR-449c-5p and ABCC1 co-transfection group was significantly increased(P＜0.05).Compared with the miR-NC+PBS group,the transplanted tumor volume in the mouse model were significantly decreased in the miR-NC+PTX group and the miR-449c-5p+PBS group(P＜0.05),and compared with the miR-NC+PTX group,the transplanted tumor volume was significantly decreased in the miR-449c-5p+PTX group(P＜0.05).Conclusion MiR-449c-5p enhanced the sensitivity of ovarian cancer to PTX by interacting with ABCC1.
万方数据
维普
