Verapamil Enhancement of Chemotherapeutic Efficacy in Human Bladder Cancer Cells

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Abstract
The calcium influx blocker verapamil has been used to overcome drug resistance in several tumor systems. The possible in vitro enhancement of drug efficacy was assessed in bladder cancer cell line T24. Combination of thiotepa and doxorubicin hydrochloride with verapamil significantly reduced the survival and growth of T24 cells after as little as 1 hour of drug exposure. An increase in doxorubicin hydrochloride-induced inhibition of [3H]thymidine uptake resulted when verapamil was administered. However, this trend was not demonstrated when combined with thiotepa. It appears that verapamil enhances thiotepa-induced cytotoxicity while it potentiates the antimitotic nature of doxorubicin hydrochloride. The data presented is consistent with the postulate that verapamil alters active efflux of drug from malignant cells and suggests that verapamil has a role in the clinical management of bladder cancer.