Effects of verapamil and S9788 on MDR-1 mRNA expression studied by in situ hybridization.

ABSTRACT

The effects of Verapamil and S9788 (triazineaminopiperidine), a new modulator of multidrug resistance, on mdr-1 mRNA expression were determined using in situ hybridization. S9788 appeared to be a better reversal drug by strongly decreasing drug efflux. However, Verapamil only decreased mdr-1 mRNA expression in Human erythroleukemic resistant cells (ADM/k562) and in Human lymphoblastic resistant cells (VLB/CEM). This effect occurred in all Verapamil-treated resistant cells with no difference between cell subpopulations. These results were confirmed by slot-blot experiments. In conclusion, S9788 and verapamil effects are comparable overall although the mechanisms responsible for this resistance modulation are not strictly identical.