Suramin, an anticancer and angiosuppressive agent, inhibits endothelial cell binding of basic fibroblast growth factor, migration, proliferation, and induction of urokinase-type plasminogen activator.
Suramin, an anticancer and angiosuppressive agent, inhibits endothelial cell binding of basic fibroblast growth factor, migration, proliferation, and induction of urokinase-type plasminogen activator.
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发表时间：
1994-05
期刊：
影响因子：
11.2
通讯作者：
S. Takano;S. Gately;M. Neville;W. Herblin;J. Gross;H. Engelhard;M. Perricone;K. Eidsvoog;S. Brem
中科院分区：
文献类型：
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作者：
S. Takano;S. Gately;M. Neville;W. Herblin;J. Gross;H. Engelhard;M. Perricone;K. Eidsvoog;S. Brem
苏拉明是目前临床试验中的抗癌剂，是生长因子（包括碱性成纤维细胞生长因子（bFGF））的药理学拮抗剂的原型。苏拉明以剂量依赖性方式抑制鸡胚绒毛尿囊膜试验中的血管生成。苏拉明，200 mg/kg静脉注射，抑制bFGF浸渍聚合物诱导的大鼠角膜血管生成;加入肝素刺激血管生成并抵消苏拉明的抑制作用。测定苏拉明对调节血管生成的关键细胞机制的半数最大抑制浓度（IC 50）：（a）bFGF与牛毛细血管内皮（BCE）细胞的低和高亲和力细胞结合，IC 50分别为24.3和71.5微克/ml;（B）牛肺动脉内皮细胞和正常AG 7680胎牛主动脉内皮细胞的自发迁移; bFGF刺激的BCE和转化的GM 7373胎牛主动脉内皮细胞的迁移，IC 50为200-320微克/ml;（c）牛肺动脉内皮细胞在> 100微克/ml时增殖，BCE细胞在> 250微克/ml时增殖;和（d）用bFGF刺激的GM 7373内皮细胞的尿激酶型纤溶酶原激活物活性，其IC 50为211微克/ml，和用bFGF刺激的BCE细胞的尿激酶型纤溶酶原激活物活性，其IC 50> 100微克/ml，而不是由佛波醇12-肉豆蔻酸酯13-乙酸酯诱导的纤溶酶原激活物活性。苏拉明抑制血管生成的多个控制点，包括那些由bFGF刺激。由于肿瘤生长依赖于血管生成，苏拉明的临床疗效可能部分与血管抑制有关。
Suramin, an anticancer agent in current clinical trials, is a prototype of a pharmacological antagonist of growth factors, including basic fibroblast growth factor (bFGF). Suramin inhibited angiogenesis in the chick chorioallantoic membrane assay in a dose-dependent fashion. Suramin, 200 mg/kg i.v., inhibited rat corneal angiogenesis induced by bFGF-impregnated polymers; addition of heparin stimulated angiogenesis and counteracted the inhibition of suramin. The half-maximal inhibitory concentration (IC50) of suramin was determined for key cellular mechanisms that regulate angiogenesis: (a) low and high affinity cellular binding of bFGF to bovine capillary endothelial (BCE) cells with IC50s, respectively, of 24.3 and 71.5 micrograms/ml; (b) spontaneous migration of bovine pulmonary artery endothelial and normal AG 7680 fetal bovine aortic endothelial cells; bFGF-stimulated migration of BCE and transformed GM 7373 fetal bovine aortic endothelial cells with IC50s of 200-320 micrograms/ml; (c) proliferation of bovine pulmonary artery endothelial cells at > 100 micrograms/ml and of BCE cells at > 250 micrograms/ml; and (d) urokinase-type plasminogen activator activity of GM 7373 endothelial cells stimulated by bFGF with an IC50 of 211 micrograms/ml and of BCE cells stimulated by bFGF at > 100 micrograms/ml, but not plasminogen activator activity induced by phorbol 12-myristate 13-acetate. Suramin inhibited multiple control points of angiogenesis, including those stimulated by bFGF. Because tumor growth is angiogenesis dependent, the clinical efficacy of suramin may relate, in part, to angiosuppression.