EFFECTS OF VERAPAMIL AND S9788 ON MDR-1 MESSENGER-RNA EXPRESSION STUDIED BY IN-SITU HYBRIDIZATION

The effects of Verapamil and S9788 (triazineaminopiperidine), a new mo dulator of multidrug resistance, on mdr-1 mRNA expression were determi ned using in situ hybridization. S9788 appeared to be a better reversa l drug by strongly decreasing drug efflux. However, Verapamil only dec reased 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 diffe rences between cell subpopulations. These results were confirmed by sl ot-blot experiments. In conclusion, S9788 and verapamil effects are co mparable overall although the mechanisms responsible for this resistan ce modulation are not strictly identical.