Staurosporine reduces P-glycoprotein expression and modulates multidrug resistance

Abstract

We have investigated the effect of staurosporine and other kinase inhibitors on the mRNA and protein levels of the P-glycoprotein (P-gp) in multidrug resistant (MDR) cells. Treatment of human MDR KB-V1 cells with staurosporine for 24 h caused up to a 50% decrease in the amount of P-gp mRNA and protein present. Co-treatment of KB-V1 cells with verapamil, a known reversal agent, plus staurosporine, H-9, or K252a resulted in an enhanced sensitization of cells to vinblastine than with verapamil alone. These findings support a role for protein kinases in the control of multidrug resistance through effects on P-gp levels.