Inhibitory effects of roxithromycin on tumor angiogenesis, growth and metastasis of mouse B16 melanoma cells.
We examined the effects of roxithromycin, a 14-membered ring macrolide antibiotic, on tumor angiogenesis, tumor growth and metastasis of mouse B16BL6 melanoma cells. The inhibitory effect of roxithromycin on angiogenesis using mouse dorsal air sac model was dose-dependent, and 100 mg/kg of roxithromycin administered intraperitoneally twice a day reduced the dense capillary network area to about 20% of the control. Administration of roxithromycin histologically reduced the development of microvessels and mononuclear cell infiltration. In vivo tumor growth studies demonstrated that intraperitoneal administration of roxithromycin at 20 mg/kg/day and 50 mg/kg/day reduced tumor size of B16BL6 melanoma to about 56% and 33% (experiment 1), 71% and 48% (experiment 2) of that in the respective controls. Roxithromycin also significantly inhibited pulmonary metastasis of B16BL6 cells in a spontaneous system. The inhibitory activities of roxithromycin on angiogenesis, tumor growth and metastasis were compared with those of a potent angiogenesis inhibitor, TNP-470. These data demonstrated that roxithromycin has potent antiangiogenic and antitumor effects and might have possible therapeutic applications.
Research Institute for Disease of the Chest, Faculty of Medicine, Kyushu University, Fukuoka, Japan. yatsunam@post.saga-med.ac.jp
J
J
Yatsunami
N
N
Tsuruta
Y
Y
Fukuno
M
M
Kawashima
S
S
Taniguchi
S
S
Hayashi
D000400:Air Sacs / Q000473:pathology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D003510:Cyclohexanes; D004305:Dose-Response Relationship, Drug; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008175:Lung Neoplasms / Q000556:secondary; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000473:pathology*; D051379:Mice; D009389:Neovascularization, Pathologic; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D015575:Roxithromycin / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D015575:Roxithromycin; D000077609:O-(Chloroacetylcarbamoyl)fumagillol