Pienta K J, Isaacs W B, Vindivich D, Coffey D S
Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
J Urol. 1991 Jan;145(1):199-202. doi: 10.1016/s0022-5347(17)38291-5.
Suramin, a new type of cancer chemotherapeutic agent with growth factor antagonist properties, has been reported to affect growth of prostate cancer metastatic lesions. Partin et al. have previously reported that prostate cancer cell motility was essential for tumor cell metastasis. We have studied the effects of suramin on cell motility and cell growth in a prostate cancer cell model. We have demonstrated that suramin has differential effects on rat prostate cancer cells in vitro. The effects of suramin on cell growth were biphasic. At low concentrations of 0.01 mM and 0.1 mM, suramin stimulated growth while it was inhibitory at a higher concentration of 1.0 mM, and 10 mM suramin resulted in cell death. Cell motility was inhibited at a suramin concentration above 0.1 mM. The inhibition of cell motility by suramin may be through the blockage of growth factor effects. Reducing serum growth factor concentration reduced cell motility and the motility was restored by the addition of basic fibroblast growth factor (bFGF) to the media. Motility which had been restored by bFGF could then be blocked by the presence of suramin. The inhibition of cell motility by suramin is reversible on washout of the drug. Suramin inhibits cell motility in both the human prostate cancer cells (LNCaP) and the rat (MLL).
苏拉明是一种新型的具有生长因子拮抗剂特性的癌症化疗药物,据报道它会影响前列腺癌转移灶的生长。帕廷等人此前曾报道,前列腺癌细胞的运动性对于肿瘤细胞转移至关重要。我们在前列腺癌细胞模型中研究了苏拉明对细胞运动性和细胞生长的影响。我们已经证明,苏拉明在体外对大鼠前列腺癌细胞有不同的影响。苏拉明对细胞生长的影响是双相的。在0.01 mM和0.1 mM的低浓度下,苏拉明刺激生长,而在1.0 mM的较高浓度下则具有抑制作用,10 mM的苏拉明导致细胞死亡。苏拉明浓度高于0.1 mM时,细胞运动性受到抑制。苏拉明对细胞运动性的抑制可能是通过阻断生长因子的作用。降低血清生长因子浓度会降低细胞运动性,而向培养基中添加碱性成纤维细胞生长因子(bFGF)可恢复运动性。bFGF恢复的运动性随后可被苏拉明的存在所阻断。苏拉明对细胞运动性的抑制在药物洗脱后是可逆的。苏拉明抑制人前列腺癌细胞(LNCaP)和大鼠前列腺癌细胞(MLL)的细胞运动性。