Suramin inhibits glioma cell proliferation in vitro and in the brain.
Suramin inhibits glioma cell proliferation in vitro and in the brain.
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苏拉明在体外和大脑中抑制神经胶质瘤细胞增殖。
DOI：
10.1007/bf01063768
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发表时间：
1994
影响因子：
3.9
通讯作者：
Brem,S
中科院分区：
文献类型：
--
作者：
Takano,S;Gately,S;Engelhard,H;Tsanaclis,AM;Brem,S
苏拉明是一种新型抗癌药物，它能阻断生长因子（包括碱性成纤维细胞生长因子（bFGF））与其受体的结合。先前的研究表明，人类和实验性胶质瘤上调并响应于bFGF的自分泌刺激，因此研究了苏拉明对胶质瘤细胞在体外和脑中的转化的抗增殖作用。苏拉明对大鼠（C6，9 L）和人（U-118，U-138，A-172，T98 G）胶质瘤细胞系的生长具有剂量依赖性抑制作用。苏拉明在250 μg/ml时显著降低培养胶质瘤细胞的溴脱氧尿苷（BUdR）标记指数，P < 0.0001。DNA流式细胞术显示苏拉明处理的胶质瘤细胞S期细胞百分比显著降低，P < 0.01。采用大鼠C6脑胶质瘤模型，腹腔注射苏拉明10-60 mg/kg，在胶质瘤和内皮细胞亚群中产生剂量依赖性的BUdR标记减少。苏拉明，200 mg/kg静脉注射，然而，导致肿瘤内转移，降低了生存率。电子显微镜显示C6胶质瘤和内皮细胞的细胞质中存在膜包涵体，这表明存在过量的糖胺聚糖。此外，用苏拉明60 mg/kg，i. p.，形成膜泡。临床相关剂量的苏拉明可显着抑制胶质瘤细胞生长和细胞动力学。肿瘤内出血的风险可能与内皮细胞损伤或抗凝剂糖胺聚糖的蓄积有关，构成了一种主要的副作用，在考虑脑内肿瘤的临床应用时应谨慎。
Suramin is a novel anticancer agent that blocks the binding of growth factors, including basic fibroblast growth factor (bFGF), to their receptors. Prior studies showed human and experimental gliomas to upregulate and respond to autocrine stimulation by bFGF, the antiproliferative effects of suramin were therefore studied on glioma cell turnoverin vitroand in the brain. Suramin inhibited the growth of rat (C6,9L) and human (U-118, U-138, A-172, T98G) glioma cell lines in a dose-dependent manner. Suramin significantly reduced the bromodeoxyuridine (BUdR) labeling index of cultured glioma cells at 250 µg/ml, P < 0.0001. DNA flow cytometry revealed a significant decrease in the percentage of suramin-treated glioma cells in S-phase, P < 0.01. Using intracerebral rat C6 glioma modelin vivo, suramin, 10–60 mg/kg, i.p., produced a dose-dependent reduction of BUdR labeling in both the glioma and endothelial cell subpopulations. Suramin, 200 mg/kg i.V., however, led to intratumoral hemorrhages that reduced survival. Electron microscopy revealed membranous inclusion bodies in the cytoplasm of C6 glioma and endothelial cells, an indication of excess glycosaminoglycans. Moreover, 46% of endothelial cells within the C6 glioma tumor treated with suramin, 60 mg/kg, i.p., developed membrane blebs. Suramin, in clinically relevant doses, significantly inhibits glioma cell growth and cytokinetics. The risk of intratumoral hemorrhage, possibly related to injury of endothelial cells or the accumulation of anticoagulant glycosaminoglycans, constitutes a major side effect and caution should be exercised in consideration of clinical application for intracerebral tumors.