Suppression of mrp1 expression and restoration of sensitivity to chemotherapy in multidrug-resistant hepatocellular carcinoma cell lines HepG2/mrp1 by RNA interference in vitro / 中华肝胆外科杂志

ABSTRACT

Objective To investigate the suppression of mrp1 and MRP1 induced by small interfering RNA and the restoration of sensitivity to chemotherapeutic drugs in the multidrug-resistant hepatocellular carcinoma cell lines HepG2/mrp1. Methods mrp1-targeted small interfering RNA duplexes were designed and composed and introduced into multidrug-resistant hepatocellular carcinoma cell lines HepG2/mrp1. The suppression of mrp1 mRNA and its gene product MRP1 was examined by RT-PCR and flow cytometry (FCM), respectively. MTT assay was performed to measure the reverse effect of small interfering RNA based on the results of ICs0. Results The overexpression of mrp1 mRNA and MRP1 was effectively suppressed by small interfering RNAs. The level of mrp1 mRNA in the transfected HepG2/mrp1 cells was reduced to (86.36±2.76)% and MRP1 to (89.38±3.76)%compared with those of the controls. The resistance to ADR was reversed five-fold, which indicated the restoration of sensitivity to drugs. Conclusion Small interfering RNA can inhibit mrp1 expression effectively and reverse the multidrug resistance mediated by MRP1.