EFFECT OF VERAPAMIL ON ADRIAMYCIN RESISTANT BLADDER TUMOR CELLS

Abstract

RBT-K5 cell line was established from a male Wistar rat bladder tumor induced with N-butyl-N-(4-hydroxybutyl) nitrosamine. RBT-K5 (ADM res.) cell line, adriamycin (ADM) resistant, was also established from RBT-K5 cells by stepwise escalation of ADM concentrations in vitro. In this study, we have examined the effect of verapamil (VR) on intracellular ADM concentration in these cell lines. The viability of RBT-K5 cells was significantly lower than that of RBT-K5 (ADM res.) at the concentration from 0.5 to 4μg/ml of ADM. The cytotoxic effect of ADM was enhanced by the addition of VR in the both cell lines. The intracellular ADM concentrations of RBT-K5 and RBT-K5 (ADM res.) were increased from 607.7±74.1ng/10⁶ cells to 1152.1±187.6ng/10⁶ cells (1.9-fold) and from 185.1±36.5ng/10⁶ cells to 751.5±258.4ng/10⁶ cells (4.1-fold), respectively, 24 hours after incubation in the presence of 10μg/ml of VR. Furthermore, the intracellular ADM concentration was maintained at high-level in combination with VR even after the removal of ADM from culture medium. These results suggest that the combination therapy with VR is more effective against ADM-resistant than ADM-sensitive bladder tumor.