[Alphastatin inhibits tumor angiogenesis in nude mice bearing human gastric cancer xenografts].
OBJECTIVE
To explore the effect and mechanism of alphastatin on tumor angiogenesis in nude mice bearing human gastric cancer xenografts.


METHODS
Nude mice were injected subcutaneously with matrigel matrix into matrigel plug. The effect of alphastatin on neovasculature inside Matrigel plug was observed. Human gastric cancer cells (BGC823) were injected subcutaneously in nude mice. After intraperitoneal injection of PBS or alphastatin,tumor volume, weight and microvascular density were analyzed. Sphingosine kinase(SPK) activity assay was used to evaluate the effect of alphastatin on tumor endothelial cells.


RESULTS
In vivo, alphastatin was sufficiently potent to suppress nude mice neovascularization. Daily administration of alphastatin produced significant tumor growth suppression [tumor volume:(612.65+/-23.45) microm(3),(1145.96+/-29.89) microm(3) vs(1771+/-31.05) microm(3) (P<0.05), tumor weight: (0.31+/-0.03) g, (0.12+/-0.02) g vs (0.67+/-0.02) g (P<0.05)]. Immunohistochemical studies of tumor tissues revealed decreased microvessel density in alphastatin-treated animals as compared with controls. Alphastatin significantly inhibited tumor endothelial cells SPK activity.


CONCLUSIONS
Alphastatin shows potent antiangiogenic properties in nude mice,which might be closely associated with down-regulation of tumor endothelial cells SPK activity.
Li
Tao
T
Department of General Surgery, General Hospital of PLA, Beijing 100853, China.
Chen
Ling
L
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D045744:Cell Line, Tumor; D005340:Fibrinogen / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; C514422:alphastatin; D005340:Fibrinogen