Verapamil and cyclosporin a sensitize human kidney tumor cells to vincristine in absence of membrane P-glycoprotein and without apparent changes in the cytoplasmic free Ca2+ concentration

Abstract

Vincristine (Vcr) dose dependently inhibited growth of the kidney adenocarcinoma cell line ACHN during 4 days of culture. Verapamil (Ver) at 10 μM and cyclosporin A (CsA) at 1 μg/ml had no effect on cell growth but significantly potentiated the action of Vcr, despite the absence of the multidrug resistance associated membrane P-glycoprotein (P-gp). Neither Ver nor CsA had any acute or long term effects on cytoplasmic free Ca2+ concentration (Ca2+i), except for a small Ver induced increase after 36 h of incubation. The results indicate that Ver and CsA may have a sensitizing effect on chemotherapeutic drug sensitivity also in absence of P-gp. However, these effects are probably not mediated by changes in Ca2+i.