Ewing M W, Liu S C, Gnarra J R, Walther M M, Meyers C E, Linehan W M
Urologic Oncology Section, Surgery Branch, NCI, National Institutes on Health, Bethesda, MD 20892.
Cancer. 1993 Feb 1;71(3 Suppl):1151-8. doi: 10.1002/1097-0142(19930201)71:3+<1151::aid-cncr2820711438>3.0.co;2-k.
Suramin is an anthelmintic drug that recently has been shown to have clinical efficacy in the treatment of patients with some advanced malignancies, including prostate carcinoma. The current study was done to assess the effect of suramin at clinically relevant doses on the growth in culture of a human prostatic carcinoma cell line, PC-3.
The antiproliferative effect of varying doses of suramin on PC-3 was assessed. Northern blot analysis was done to assess the potential changes in genetic expression at different times after the initiation of treatment.
Suramin inhibited the proliferation of PC-3 in a dose-related manner (concentration range, 30-300 microM). Compared with fetal calf serum 2%, when the cells were grown in fetal calf serum 10%, higher concentrations of suramin were required to inhibit tritiated thymidine incorporation. When grown in RPMI without supplement, the PC-3 cell number remained the same. When 100 microM suramin was included, the cell number decreased. By contrast, when RPMI was supplemented with insulin, transferrin, and selenium (ITS), PC-3 grew well. The inhibition of the proliferation of PC-3 cells by suramin was decreased when ITS were added to the cells grown under serum-free conditions.
These results were consistent with the hypothesis that in vitro inhibition of the growth of PC-3 cells by suramin may be caused, at least in part, by the growth factor antagonism of the drug. In fetal calf serum 2%, the suramin inhibition was reversible after 3 days. If the treatment was extended to 6 days, however, the PC-3 cells were unable to recover. Cell-cycle analysis revealed that, after 6 days of treatment, there was a decrease in the number of cells in G1 that corresponded with an increased number of cells in G2/M. This suggested that critical antineoplastic events were occurring during this time. Molecular analysis did not detect any altered expression of actin, transforming growth factors alpha or beta, or histone compared with untreated control samples.
苏拉明是一种驱虫药，最近已显示在治疗包括前列腺癌在内的一些晚期恶性肿瘤患者中具有临床疗效。当前的研究旨在评估临床相关剂量的苏拉明对人前列腺癌细胞系PC-3培养生长的影响。
评估不同剂量的苏拉明对PC-3的抗增殖作用。进行Northern印迹分析以评估治疗开始后不同时间基因表达的潜在变化。
苏拉明以剂量相关的方式抑制PC-3的增殖（浓度范围为30 - 300 microM）。与2%胎牛血清相比，当细胞在10%胎牛血清中生长时，需要更高浓度的苏拉明来抑制氚标记胸腺嘧啶核苷掺入。在无补充剂的RPMI中生长时，PC-3细胞数量保持不变。当加入100 microM苏拉明时，细胞数量减少。相比之下，当RPMI补充胰岛素、转铁蛋白和硒（ITS）时，PC-3生长良好。当向无血清条件下生长的细胞中添加ITS时，苏拉明对PC-3细胞增殖的抑制作用降低。
这些结果与以下假设一致，即苏拉明在体外对PC-3细胞生长的抑制可能至少部分是由该药物的生长因子拮抗作用引起的。在2%胎牛血清中，苏拉明的抑制作用在3天后是可逆的。然而，如果治疗延长至6天，PC-3细胞无法恢复。细胞周期分析显示，治疗6天后，G1期细胞数量减少，相应地G2/M期细胞数量增加。这表明在此期间发生了关键的抗肿瘤事件。与未处理的对照样品相比，分子分析未检测到肌动蛋白、转化生长因子α或β或组蛋白的表达有任何改变。
