Effects of vinblastine, colchicine, and verapamil on rhodamine 123 accumulation in human P-glycoprotein-positive leukemia cells.

Multidrug-resistant (MDR) cells have been characterized by reduced accumulation of rhodamine 123 (R123). We addressed the question of whether R123 could compete with substrates or inhibitors (vinblastine, colchicine, verapamil) of P-glycoprotein (Pgp) overexpressed in MDR cells, using fluorescence image cytometry. Verapamil caused a dose-dependent increase in R123 accumulation. R123 accumulation was increased by vinblastine only at high levels and colchicine had no effect on R123 accumulation. Treatments with two drugs altered R123 accumulation depending on drug concentration ratio. The results indicate that vinblastine, R123 and verapamil can compete for outward transport by Pgp. A dual effect of vinblastine suggests that vinblastine can activate Pgp at low concentrations and inhibit R123 transport at higher concentrations.