VASOACTING AGENTS FLAVONE ACETIC-ACID AND HYDRALAZINE GIVEN IN COMBINATION ENHANCE ANTITUMOR EFFECTS UNDER CONDITION OF HYPERTHERMIA

The combined effects of flavone acetic acid (FAA), hydralazine (HYD) a nd hyperthermia on B16 melanoma cells and solid tumor were examined in vitro and in vivo. In vitro, hyperthermia did not enhance the cytotox icity of the combined use of FAA and HYD. In vivo, growth inhibition o f B16 melanoma solid tumor by FAA (150 mg/kg) combined with HYD (5.0 m g/kg) could not be differentiated from that by FAA or HYD alone. Incre ased antitumor effect was recognized when FAA combined with HYD was us ed under conditions of hyperthermia. FAA combined with HYD significant ly reduced tumor blood flow compared to FAA alone or HYD alone. We thu s conclude that the significant reduction in tumor blood flow may play an important role in the enhanced antitumor effects of the combined t reatment with FAA, HYD, and hyperthermia.