MEK Inhibitor Enhances Sensitivity To Chemotherapeutic Drugs In Multidrug Resistant Hepatocellular Carcinoma Cells

Objectives To explore the relationship between the MAPK signal transduction pathwayand multidrug resistance in hepatocellular carcinoma cells.Methods CCK-8assay was used to determine drug sensitivity of HepG2andHepG2/ADM in combination U0126.Flow cytometry was employed to analyze the rate ofapoptosis. Real-time quantitative RT-PCR was used to detect different concentrations ofU0126treatment of P-gp and MRP1mRNA expression. P-gp and MRP1expression levelswere measured by Western blot.Results IC50value was remarkably decreased in combination U0126. Quantitativereal-time PCR results revealed that the expression of MDR1(MRP1) for HepG2/ADMwere5.37-fold (6.14) higher than HepG2cells, compared with parental cells,. And theexpression of HepG2/ADM was decreased under the treatment of U0126in dose-dependentmanner. Furthermore, the expression of P-gp(MRP1) for HepG2/ADM were2.68-fold(2.76)higher than HepG2cells. And the expression levels were decreased under the treatment ofU0126in dose-dependent manner.Conclusion The experiment shows that MEK inhibitor U0126can enhance sensitivity tochemotherapeutic drugs by down-regulation of P-gp and MRP1expression in resistanthepatocellular carcinoma cells. The combination of MEK inhibitor and conventionalchemotherapy drugs for the treatment of drug-resistant hepatocellular carcinoma cells mayprovide new therapeutic prospects.