摘要
寻找新的血管生成抑制剂，探讨其抗肿瘤转移作用及机理。方法利用鸡胚尿囊膜模型，观察抗肿瘤抗生素Ｃ１０２７对血管生成的抑制作用。经静脉途径给予Ｃ１０２７和丝裂霉素治疗，比较二者对小鼠Ｌｅｗｉｓ癌自发性肺转移的影响；同时进行受体结合分析，观察碱性成纤维细胞生长因子（ｂＦＧＦ）受体是否为Ｃ１０２７作用的靶点。结果Ｃ１０２７有很强的抑制血管生成作用，在低剂量（０．０１μｇ／鸡胚）即可抑制鸡胚尿囊膜的血管生成，并且可以阻断ｂＦＧＦ与受体蛋白结合，其半数有效抑制浓度（ＩＣ５０）为２．３×１０－６μｇ／ｍｌ。采用等毒性剂量进行比较：Ｃ１０２７（０．１ｍｇ／ｋｇ）和丝裂霉素（１．２５ｍｇ／ｋｇ）对小鼠Ｌｅｗｉｓ癌的肺转移抑制率分别为９８％和７８％，对皮下肿瘤的抑制率分别为８６％和５０％，前者明显高于后者。结论Ｃ１０２７是一种很强的血管生成抑制剂，可能以ｂＦＧＦ的受体为作用靶点，抑制血管生成，并阻断小鼠Ｌｅｗｉｓ癌的自发性肺转移。
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.
出处
《中华医学杂志》
CAS
CSCD
北大核心
1997年第9期657-660,共4页
National Medical Journal of China
基金
国家自然科学基金
