Suramin inhibits bFGF-induced endothelial cell proliferation and angiogenesis in the chick chorioallantoic membrane.
Suramin inhibits bFGF-induced endothelial cell proliferation and angiogenesis in the chick chorioallantoic membrane.
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DOI：
10.1038/bjc.1993.457
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发表时间：
1993-11
影响因子：
8.8
通讯作者：
Del Tacca, M
中科院分区：
文献类型：
--
作者：
Danesi, R;Del Bianchi, S;Soldani, P;Campagni, A;La Rocca, R V;Myers, C E;Paparelli, A;Del Tacca, M
观察了生长因子有丝分裂活性抑制剂苏拉明对碱性成纤维细胞生长因子(BFGF)诱导的牛主动脉内皮细胞增殖和鸡胚绒毛尿囊膜(CAM)血管生成的影响。用反义寡核苷酸检测bFGF基因表达在内皮细胞生长中的作用。体外培养的内皮细胞在10 ng·ml~(-1)的碱性成纤维细胞生长因子刺激下，[~3H]-胸腺嘧啶核苷摄取量增加了4倍，苏拉明300微克·ml~(-1)可抑制这种增加。碱性成纤维细胞生长因子反义寡聚物(10微米)可使指数生长细胞的[~3H]-胸腺嘧啶核苷掺入减少76%；这种作用可被bFGF10ngml-1逆转。在鸡胚的CAM中，苏拉明50微克是一种比肝素60微克/氢化可的松50微克组合更有效的血管生成抑制物，苏拉明处理组的血管减少面积(2.4cm2)明显大于肝素/氢化可的松组(0.6cm2)，而血管密度的减少与对照组相似(分别为-35%和-29%)。总之，bFGF和bFGF反义寡核苷酸的处理结果表明，bFGF在内皮细胞增殖中起着相关的作用，并且可能是苏拉明的靶点，因为该药物能够抑制基础和bFGF诱导的内皮细胞的生长；除此之外，苏拉明在CAM中是一种比肝素/氢化可的松更有效的血管生成抑制剂。
The effects of suramin, an inhibitor of growth factor mitogenic activity, were evaluated on basic fibroblast growth factor (bFGF)-induced proliferation of bovine aortic endothelial cells and on angiogenesis in the chorioallantoic membrane (CAM) of chick embryos. The role of bFGF gene expression in endothelial cell growth was also investigated by using an antisense oligodeoxynucleotide to bFGF. The 4-fold increase in [3H]-thymidine uptake in endothelial cells in vitro upon stimulation with 10 ng ml-1 of bFGF was inhibited by suramin 300 micrograms ml-1. bFGF antisense oligomer (10 microM) reduced [3H]-thymidine incorporation in exponentially growing cells by 76%; this effect was reversed by bFGF 10 ng ml-1. In the CAM of chick embryos suramin 50 micrograms was a more potent inhibitor of angiogenesis than the combination of heparin 60 micrograms/hydrocortisone 50 micrograms; the mean value of the area with reduced vascularity was significantly larger in suramin-treated CAMs (2.4 cm2) than in heparin/hydrocortisone (0.6 cm2), while the reduction of vascular density was similar (- 35 and - 29% compared to controls, respectively), In conclusion, the effects of treatments with bFGF and bFGF antisense oligomer demonstrate that bFGF plays a relevant role in endothelial cell proliferation and may be the target of suramin since the drug is able to suppress basal and bFGF-induced endothelial cell growth; in addition to this, suramin is a more potent angiogenesis inhibitor in the CAM than the combination of heparin/hydrocortisone.