Inhibition of tumor angiogenesis by roxithromycin, a 14-membered ring macrolide antibiotic.
We examined the effects of roxithromycin, a 14-membered ring macrolide antibiotic, on tumor angiogenesis using a mouse dorsal air sac model. The inhibitory effect of roxithromycin 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. However, at concentrations of up to 50 microM, roxithromycin had no effect on lung cancer cells and human vascular endothelial cell growth and lung cancer cell production of the angiogenesis-inducing factors interleukin-8 and vascular endothelial growth factor. Roxithromycin at concentrations greater than 20 microM inhibited endothelial cell migration and tube formation.
Yatsunami
J
J
Research Institute for Disease of the Chest, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Tsuruta
N
N
Hara
N
N
Hayashi
S
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000098:blood supply; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D016228:Endothelial Growth Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007797:Laminin; D008175:Lung Neoplasms / Q000098:blood supply* / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011509:Proteoglycans; D015575:Roxithromycin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D016228:Endothelial Growth Factors; D016209:Interleukin-8; D007797:Laminin; D008222:Lymphokines; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C059485:matrigel; D015575:Roxithromycin; D003094:Collagen