title: Roxithromycin inhibits angiogenesis of human hepatoma cells in vivo by suppressing VEGF production.
abstract: BACKGROUND
  Recently, 14-member macrolide antibiotics such as Clarithromycin and Roxithromycin (RXM) have been shown to have anti-cancer and anti-angiogeneic effects. However, it is not fully understood whether and how RXM suppresses angiogenesis in human hepatoma, which is a well-known hypervascular tumor.
  
  
  METHODS
  In the present study, we examined the effects of RXM on tumor angiogenesis in the human hepatoma cell line, HepG2. In vivo, angiogenesis was examined using a mouse dorsal air sac model.
  
  
  RESULTS
  The inhibitory effect of RXM was dose-dependent and the angiogenesis index of 100mg/kg/day of RXM administered intraperitoneally twice a day was significantly lower than the control. Next, we examined the effect of RXM on vascular endothelial growth factor (VEGF) mRNA expression and its protein level in HepG2 cells. When 100 microM of RXM were added, VEGF mRNA expression in HepG cells was inhibited and its protein level reduced.
  
  
  CONCLUSIONS
  These results suggest that RXM inhibits tumor angiogenesis in human hepatoma, and that VEGF alteration may be involved in the mechanism of this inhibitory effect. Because RXM is widely used in clinical practice, it may represent an effective new strategy for human hepatoma therapy.
authors.affiliation: Department of Surgical Oncology and Digestive Surgery, Kagoshima University, School of Medicine, Kagoshima, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Aoki
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ueno
authors.forename: Fumitake
authors.initials: F
authors.lastname: Kubo
authors.forename: Tohru
authors.initials: T
authors.lastname: Oyama
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sakuta
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsushita
authors.forename: Ikuro
authors.initials: I
authors.lastname: Maruyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Aikou
mesh_terms: D000400:Air Sacs / Q000098:blood supply; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000188:drug therapy; D048708:Cell Growth Processes / Q000187:drug effects; D003510:Cyclohexanes; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply* / Q000188:drug therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015575:Roxithromycin / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics
chemical_list: D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D012333:RNA, Messenger; D012717:Sesquiterpenes; D042461:Vascular Endothelial Growth Factor A; D015575:Roxithromycin; D000077609:O-(Chloroacetylcarbamoyl)fumagillol