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) and hyperthermia on B16 melanoma cells and solid tumor were examined in vitro and in vivo. In vitro, hyperthermia did not enhance the cytotoxicity of the combined use of FAA and HYD. In vivo, growth inhibition of B16 melanoma solid tumor by FAA (150 mg/kg) combined with HYD (5.0 mg/kg) could not be differentiated from that by FAA or HYD alone. Increased antitumor effect was recognized when FAA combined with HYD was used under conditions of hyperthermia. FAA combined with HYD significantly reduced tumor blood flow compared to FAA alone or HYD alone. We thus conclude that the significant reduction in tumor blood flow may play an important role in the enhanced antitumor effects of the combined treatment with FAA, HYD, and hyperthermia.
Yamamoto
M
M
Cancer Center of Kyushu University Hospital, Fukuoka, Japan.
Kusumoto
T
T
Endo
K
K
Baba
H
H
Sakaguchi
Y
Y
Maehara
Y
Y
Sugimachi
K
K
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D003131:Combined Modality Therapy; D005419:Flavonoids / Q000008:administration & dosage; D006830:Hydralazine / Q000008:administration & dosage; D006979:Hyperthermia, Induced; D008297:Male; D008546:Melanoma, Experimental / Q000098:blood supply / Q000188:drug therapy / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014665:Vasodilator Agents / Q000008:administration & dosage
D005419:Flavonoids; D014665:Vasodilator Agents; D006830:Hydralazine; C049328:flavone acetic acid