Enhancement of antitumor activity of bleomycin A5 in mouse sarcoma 180 cells in vitro and in vivo by verapamil

Verapamil (Ver), a calcium influx blocker, enhanced the cytotoxicity of bleomycin A5 (BLM) in cultured S-180 cells. IC50 of BLM to the cells was about 2.6 micrograms/ml when the cells were treated with BLM alone, but when the cells were treated with BLM plus Ver 1, 5, 10 micrograms/ml, the IC50 were 1/1.2, 1/5.2, 1/7.4 of the cells treated with BLM alone, respectively. In colony test, the survival fractions of the cells treated with BLM 20, 60, 100 micrograms/ml plus Ver 60 micrograms/ml were 1/7, 1/8, 1/11 of the cells treated with BLM alone, respectively. Ver enhanced the growth inhibitory actions of BLM in mice bearing S-180 sarcoma by 60% or over. The mean survival the growth inhibitory actions of BLM in mice bearing S-180 sarcoma by 60% or over. The mean survival time of the mice bearing S-180 ascites sarcoma treated with BLM plus Ver was prolonged 21% from that of the mice treated with BLM alone. The results suggest that Ver may be used clinically as an antitumor enhancer of BLM.