Roxithromycin inhibits angiogenesis of human hepatoma cells in vivo by suppressing VEGF production.
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.
Aoki
Dai
D
Department of Surgical Oncology and Digestive Surgery, Kagoshima University, School of Medicine, Kagoshima, Japan.
Ueno
Shinichi
S
Kubo
Fumitake
F
Oyama
Tohru
T
Sakuta
Tetsuya
T
Matsushita
Kenji
K
Maruyama
Ikuro
I
Aikou
Takashi
T
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
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D012333:RNA, Messenger; D012717:Sesquiterpenes; D042461:Vascular Endothelial Growth Factor A; D015575:Roxithromycin; D000077609:O-(Chloroacetylcarbamoyl)fumagillol