Inhibition growth of multidrug resistant KBV200 cells by MDR1 antisense RNA

Acquisition of resistance to multiple drugs of tumor cell caused by overexpression of the MDR1 gene is one of major obstacles in cancer chemotherapy. We have attempted to reverse the multidrug resistance (MDR) phenotype by treating vincristine (VCR) and adriamycin (ADM) resistant KBV200 cells with MDR1 antisense RNA. Retroviral vector expressing the antisense RNA was transfected into KBV200. In the transfected cells, a stable expression of antisense RNA and a reduction of cellular MDR1 mRNA could be detected by RT-PCR, and a reduction of MDR1 specific P-glycoprotein (P-gp) was also detected by Western blot, whereas an increase of the drug concentration in the cells was detected by FAGS, The IC50 Of transfected cells to VCR and ADM was reduced by 65 and 47%. This study demonstrates that antisense RNA can increase the sensitivity of tumor cells to anticancer drug by decreasing the expression of the MDR1 gene. This strategy may be applicable to cure cancer patients with P-gp mediated MDR phenotype. (C) 1997 Academic Press.