[Improvement of cancer therapy by angiotensin II-induced hypertension chemotherapy]

Angiotensin II-induced hypertension chemotherapy using cis-diamminedichloroplatinum (II) (DDP) or carboquone (CQ), and a modification of the therapy through combination with a cardiotonic, such as aminophylline (AP) and trans-pi-oxocamphor (pi OC), were compared with regard to therapeutic efficacy on an established mouse mammary carcinoma grown s.c. in syngeneic mice. The hypertension chemotherapy proved to be more effective than conventional administration with the anticancer drug alone. On the other hand, a remarkable improvement in antitumor effect without any increase in the general toxicity was more apparent in the modified hypertension chemotherapy than in angiotensin II hypertension chemotherapy. The combination therapy using DDP, AP or pi OC, but not AT-II, did not produce any increase in antitumor effect as compared to conventional administration with anticancer drug alone. The cytotoxicity of DDP against cultured HeLa cells was not enhanced by co-administration with AT-II, AP and/or pi OC. Thus, the increase in the therapeutic efficacy obtained by the modified hypertension chemotherapy may be attributable to the specific augmentation in delivery of the anticancer drug to the tumor tissue, but not to any specific enhancement in the cytotoxicity of the anticancer drug against to the tumor cells.