Verapamil enhancement of the antitumour effect of cis-diammionedichloroplatinum(II) in mice bearing Ehrlich ascites carcinoma cells

The calcium channel blocker verapamil, which possesses coronary vasodilator activity, greatly enhanced the cytotoxic activity of cisplatin against the growth of Ehrlich ascites carcinoma cells. Tumour-bearing mice treated with cisplatin (3.5 mg kg(-1), single i.p.) showed a 29.5 days mean survival time with 40% long-term survivors. However, pre-treatment with verapamil 20 mg kg(-1), twice daily for 5 days before cisplatin increased the long-term survivors to 60% with a mean survival time of 43.4 days. Verapamil pre-treatment increased the uptake of platinum into tumour cells, with greater toxicity and marked alteration of the tumour cell cycle. Treatment with cisplatin and cisplatin plus verapamil showed marked accumulation of the cells in S-phase with more depletion of G(0)/G(1) phase. This study may suggest the benefits of using verapamil with cisplatin against tumour cells.