[Inhibition of angiogenesis by antitumor antibiotic C1027 and its effect on tumor metastasis].
OBJECTIVE
To investigate the effect of C1027, an enediyne antitumor antibiotic, on angiogenesis and its anti-metastatic activity.


METHODS
Chick embryo chorioallantoic membrane assay was used for anti-angiogenesis activity and bFGF receptor binding assay was used for the elucidation of the possible mechanism. Spontaneous pulmonary metastasis of Lewis carcinoma in mice was employed to evaluate the anti-metastatic effect.


RESULTS
C1027 was highly potent in suppressing angiogenesis with a minimum effective dose of 0.01 microgram/egg. Enediyne chromophore moiety of the C1027 molecule was essential to anti-angiogenesis activity. Receptor binding assay showed that C1027 blocked bFGF binding to its receptor with an IC50 value of 2.3 x 10(-6) micrograms/ml. C1027 markedly inhibited pulmonary metastasis of Lewis carcinoma in mice. Compared at equitoxic dosage level (1/4 LD50), C1027 (0.01 mg/kg, i.v., x 2) was more effective than mitomycin (1.25 mg/kg, i.v., x 2) and the percent inhibition of metastatic foci in the lung was 98% and 78%, respectively.


CONCLUSIONS
C1027 is a new potent anti-angiogenesis agent with markedly anti-metastatic activity. The mechanism of C1027 suppressing angiogenesis may be related to its blocking effect on bFGF binding to its receptor.
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing.
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D000617:Aminoglycosides; D043925:Angiogenesis Inducing Agents / Q000037:antagonists & inhibitors*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000473:pathology*; D002642:Chick Embryo; D053281:Enediynes; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009368:Neoplasm Transplantation; D051381:Rats; D017208:Rats, Wistar; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism
D000617:Aminoglycosides; D043925:Angiogenesis Inducing Agents; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D053281:Enediynes; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; C058024:C 1027