[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.
Zhen
H
H
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing.
Xue
Y
Y
Zhen
Y
Y
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