Effect of KN-62, Ca2+/calmodulin-dependent protein kinase II inhibitor, on adriamycin resistance of human ovarian cancer cells.

We examined effects of an isoquinolinesulfonamide derivative, KN-62, on human ovarian cancer cells, NOS3AR, that are resistant to Adriamycin (ADR). MTT assay revealed that 10 microM KN-62 overcame the resistance. KN-62 had little effect on GST activity. In studies on the intracellular accumulation of ADR, KN-62 increased the ADR contents in the resistant cells close to the level seen in the sensitive cells. These results suggest that the reversal of the resistance against ADR in ovarian cancer cells by KN-62 is mainly due to higher accumulation of ADR in NOS3AR cells. Furthermore, we detected Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) in NOS3AR cells since KN-62 is a specific inhibitor of the kinase. In this paper, we discussed on modulation of ADR-resistance by KN-62.