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 anti biotic, on tumor angiogenesis, tumor growth and metastasis of mouse B16BL6 melanoma cells. The inhibitory effect of roxithromycin on angiogenesis usin g mouse dorsal air sac model was dose-dependent, and 100 mg/kg of roxithrom ycin 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 intraperitone al 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 spontaneo us system. The inhibitory activities of roxithromycin on angiogenesis, tumo r growth and metastasis were compared with those of a potent angiogenesis i nhibitor, TNP-470. These data demonstrated that roxithromycin has potent an tiangiogenic and antitumor effects and might have possible therapeutic appl ications.