We have examined the enhancing effect of verapamil on the cytotoxicity of vincristine (VCR), adriamycin (ADM) and cis-platinum (CDDP) against the established cell line from human renal cell carcinoma (NUR) and primary human kidney cell (PHK). To test the effect of cytotoxicity, we have assayed cell growth curve and 3H-thymidine incorporation. And effects of verapamil on the uptake and release of anticancer drugs were examined by measurement of cellular radioactivity of 3H-VCR and 3

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... The concentration of verapamil using anticancer drugs was 1.0cg/ml which itself showed no cytotoxicity. The results we obtained were as follows: 1) Verapamil showed enhanced cytotoxicity of ADM, VCR and CDDP in the growth curve and reduced the 3H-thymidine incorporation for NUR cell. The concentration of verapamil which could enhance the cytotoxicity of ADM against NUR cell was proved to be 0. lg/ml and over. 2) The IC50 of ADM, VCR and CDDP for NUR cell by 3H-thymidine incorporation were 0.095, 4.81 and 1.01pg/ml, respectively, while in the presence of verapamil (1.0pg/ml) the IC50 were shifted to 0.039, 1.29 and 0.508pg/ml, respectively. 3) By verapamil, the uptake of 3H-VCR and 3H-daunomycin into NUR cells were increased and the release of 3H-VCR from NUR cells was also inhibited. But verapamil had no effect on the release of 3 H-daunomycin from NUR cells. 4) In PHK cell, we observed a slight enhancing effect of verapamil on the cytotoxicity of VCR, ADM and CDDP, but the degree was so slight that it seemed to be able to ignore. The uptake of 3H-VCR and 3H-daunomycin into PHK cells showed a small increase by verapamil.