Verapamil enhanced in vitro chemosensitivity of a murine bladder carcinoma, FCB.
The in vitro enhancement of chemotherapeutic efficacy by verapamil, a calcium antagonist, was assessed using FCB, a transplantable murine transitional cell carcinoma. Exponentially growing FCB cells were partially resistant to treatment with both thiotepa (10(-4) M) and Adriamycin (10(-5) M), however, there was a significant reduction in cell growth when either agent was administered in combination with verapamil (10(-5) M); the effect was evident over a wide range of drug concentrations (10(-4) - 10(-9) M). There was also a pronounced inhibition of DNA precursor incorporation when verapamil was used in combination with either agent. Fluorometric analysis of Adriamycin uptake indicated that verapamil caused an increase in the intracellular concentration of the agent. The data presented are consistent with the postulate that verapamil enhances chemotherapeutic efficacy by altering cellular permeability to the cytotoxic agents. Our study indicates that the use of verapamil in combination with cytotoxic agents for intravesical chemotherapy of bladder tumors may prove to be beneficial in human patients.
D000818:Animals; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000503:physiopathology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D013852:Thiotepa / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D014700:Verapamil / Q000494:pharmacology*
D004317:Doxorubicin; D013852:Thiotepa; D014700:Verapamil; D013936:Thymidine