Reversing effect of multidrug resistance in hepatocellular carcinoma engineering cell line with antisence RNA

【Objective】To investigate the reversal effect of multidrug resistance with antisense RNA of mdr1 gene delivered by recombinant adenoviruses in human engineering HCC cell line HepG2/R.【Methods】The recombinant adenoviruse was transfected into the engineering cell line HepG2/R.In order to investgate the reversal of the multidrug resistance phenotype, the expression of mdr1 mRNA was measured by RT-PCR, the production of P-glycoprotein and the accumulation of the daunorubicin(DNR) was determinated by flow cytometry.The sensitivitie of adriamycin(ADM) for HepG2/R cells was examined by MTT analysis.【Results】Compared with the parental HepG2 cells expressing low-level mdr1 mRNA and P-glycoprotein, engineering cell line HepG2/R was only stably expressing mdr1 gene and P-glycoprotion.The transfection of antisence RNA into HepG2/R cells resulted in decreases of mdr1 mRNA and P-glycoprotein levels.The sensitivity of transfected HepG2/R cells to ADM was reduced from 25μg/mL to 3μg/mL in IC50 level.The DNR accumulation was increased in transfected HepG2/R cells.ConclusionThis study demonstrates that mdr1 antisense RNA can increase the sensitivities of HepG2/R cells to anticancer drug by decreasing the expression of the mdr1 gene and inhibiting P-glycoprotein expression.