Correlation Between Y-box Binding Protein-1 Expression and P-Glycoprotein in Drug-resistant Hepatocellular Carcinoma Bel-7402/ADM Cells / 医药导报

ABSTRACT

Objective To explore the correlation between Y-box binding protein-1 ( YB-1) and P-glycoprotein ( P-gp) in drug-resistant hepatocellular carcinoma ( HCC) Bel-7402/ADM cells, and speculate the related mechanism of drug resistance.Methods Bel-7402/ADM cells were developed by concentration gradient escalation and intermittent administration of large dose. The levels of YB-1 mRNA and MDR1 mRNA were detected by means of RT-PCR.Western blotting was used to detect the protein expression of YB-1 and P-gp in the Bel-7402 cells and doxorubicin resistant Bel-7402 ( Bel-7402/ADM) cells. Bel-7402/ADM cells were transfected with small interfering RNA ( siRNA) targeting human YB-1. Expression levels of YB-1 and MDR1 mRNA and protein were detected by means of RT-PCR and Western blotting. Results IC50 values of ADM on hepatoma carcinoma cells Bel-7402 and Bel-7402/ADM were (2.23±0.07) and (7.02±0.03) μmol?L-1. The mRNA expression levels of MDR1 and YB-1 were all significantly higher in Bel-7402/ADM cells than in Bel-7402 ( P<0.01) . The mRNA expression levels of MDR1 and YB-1 in Bel-7402/ADM cells transfected with YB-1 siRNA were reduced significantly (P<0.01). The protein levels of YB-1 and MDR1 in Bel-7402/ADM cells transfected with YB-1 siRNA were reduced significantly ( P<0. 05 ) . Conclusion These results suggest that the high expression level of YB-1 is probably correlated with multidrug resistance in HCC Bel-7402/ADM cells.