Inhibition of angiogenesis by antitumor antibiotic C1027 and its effect on tumor metastasis.  

作　　者：Zhen Hongying, Xue Yuchuan, Zhen Yongsu. Instutute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. 

出　　处：《Chinese Medical Journal》1998年第1期62-62,共1页中华医学杂志（英文版）

摘　　要：Abstract 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 μg/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 IC 50 value of 2.3×10 -6 μg/ml. C1027 markedly inhibited pulmonary metastasis of Lewis carcinoma in mice. Compared at equitoxic dosage level (1/4 LD 50 ), C1027 (0.01 mg/kg, iv, x 2) was more effective than mitomycin (1.25 mg/kg, iv, 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.Abstract 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 μg/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 IC 50 value of 2.3×10 -6 μg/ml. C1027 markedly inhibited pulmonary metastasis of Lewis carcinoma in mice. Compared at equitoxic dosage level (1/4 LD 50 ), C1027 (0.01 mg/kg, iv, x 2) was more effective than mitomycin (1.25 mg/kg, iv, 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.

关 键 词：ANTITUMOR ANGIOGENESIS METASTASIS antibiotic INHIBITION 

分 类 号：R730.2[医药卫生—肿瘤]