Effects of Changweiqing on nuclear translocation of Y-box binding protein-1 and expression of P-glycoprotein in human colon cancer cell line with drug-resistance induced by vincristine.

Objective To evaluate the effects and molecular mechanism of action of Changweiqing (CWQ)in reversing multidrug resistance by observing its impacts on nuclear translocation of Y-box binding protein -1(YB-1),multi-drug resistance gene(MDR1)expression and P-glycoprotein(P-gp)expression in human colon cancer cell line HCT8/V with drug-resistance induced by vincristine.Methods Cultured HCT8/V cells were exposed to the CWQ-containing rat serum prepared by drug perfusion.YB-1 expressions in cell plasma and nuclei were examined by Western blot;the binding activity of YB-1 to MDR1 gene promoter sequences was detected by electrophoretic mobility shift assay(EMSA);the mRNA transcription levels of MDR1,YB-1 and multi-resistance related protein(MRP)were examined by RT-PCR;the expression of P-gp on cell membrane was determined by flow cytometry.Results Along with the increasing drug's concentration of CWQ-containing serum from 1.25%up to 2.5%and 5%,the expressions of YB-1 decreased in HCT8/V cell nuclear and increased in cytoplasm gradually;the binding activity of YB-1 to MDR1 gene promoter weakened(P0.01),MDR1 mRNA expression and fluorescence intensity of P-gp on cell membrane attenuated(P0.05 or P0.01),while YB-1 and MRP mRNA unchanged(P0.05).Conclusion CWQ could reverse the drug-resistance of colon cancer cells by influencing nuclear translocation of YB-1 and reducing the expression of MDR1/P-gp.