Wade T P, Kasid A, Stein C A, LaRocca R V, Sargent E R, Gomella L G, Myers C E, Linehan W M
National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
J Surg Res. 1992 Aug;53(2):195-8. doi: 10.1016/0022-4804(92)90034-w.
Suramin is a polyanionic compound used clinically for the treatment of trypanosomiasis, which is known to inhibit the action of many protein factors in vitro. Transforming growth factor-beta (TGF-beta) is a multifunctional regulatory protein which inhibits the growth of renal cell carcinoma in culture. While suramin at 50-500 micrograms/ml had no significant effect on the growth of renal cell carcinoma in culture in our experiments, it did partially reverse the growth inhibition induced by TGF-beta in the two cell lines tested. This effect apparently is caused by suramin's direct interference with 125I-labeled TGF-beta's ability to bind to the cell, and not by any effect of suramin on the TGF-beta receptor. Furthermore, suramin dissociates TGF-beta bound to the cell with a t1/2 of less than 30 min. These results are consistent with those previously reported regarding suramin's interaction with other protein growth factors, and suggest that suramin may interact with the TGF-beta protein itself to inactivate it.
苏拉明是一种多阴离子化合物,临床上用于治疗锥虫病,已知它在体外能抑制多种蛋白质因子的作用。转化生长因子-β(TGF-β)是一种多功能调节蛋白,在培养中可抑制肾细胞癌的生长。在我们的实验中,50 - 500微克/毫升的苏拉明对培养的肾细胞癌生长没有显著影响,但它确实部分逆转了所测试的两种细胞系中由TGF-β诱导的生长抑制。这种效应显然是由苏拉明直接干扰125I标记的TGF-β与细胞结合的能力引起的,而不是苏拉明对TGF-β受体有任何影响。此外,苏拉明以小于30分钟的半衰期使与细胞结合的TGF-β解离。这些结果与先前报道的关于苏拉明与其他蛋白质生长因子相互作用的结果一致,并表明苏拉明可能与TGF-β蛋白本身相互作用使其失活。