Fujiuchi S, Ohsaki Y, Kikuchi K
First Department of Medicine, Asahikawa Medical College, Japan.
Oncology. 1997 Mar-Apr;54(2):134-40. doi: 10.1159/000227677.
The epidermal growth factor (EGF) is a potent growth factor that is believed to enhance the proliferation of cancer cells by a paracrine or autocrine mechanism. EGF transduces various signals and finally stimulates cell proliferation upon binding to cell surface receptors. Prevention of the association of this peptide with its receptors might lead to the development of new modalities for treatment of lung cancer. Several investigators have reported that suramin has antiproliferative activity against cancer cells that express EGF receptors (EGF-R), and that it acts by blocking the binding of the ligand to its receptor. In this study, we analyzed the antitumor effect of suramin using two lines of lung cancer cells (A549 and PC-13), which express EGF-R, and a variety of assays. Receptor-binding assays confirmed that A549 and PC-13 cells have cell surface receptors for EGF. Suramin inhibited the binding of EGF to these receptors. EGF and fetal bovine serum (FBS) stimulated the proliferation of cells, but suramin inhibited these effects in a dose-dependent fashion. Suramin at 200 microg/ml reduced the growth of A549 and PC-13 cells by 25 and 15%, respectively, in medium that contained 1% FBS. Paradoxically, the concentrations of suramin that inhibited cell proliferation were lower than those that were effective in inhibiting the binding of EGF to its receptor. Although expression of c-fos and c-myc mRNA increased when cells were stimulated by EGF or FBS, suramin at 200 microg/ml did not markedly alter such expression. Suramin partially blocked the EGF-induced progression of the cell cycle from the G0/G1 to the S phase. These results suggest that suramin partially blocks EGF signal transduction. Suramin probably inhibits cell proliferation by inhibiting intranuclear enzymes, as well as by partial blockage of EGF signal transduction.
表皮生长因子（EGF）是一种强效生长因子，据信它通过旁分泌或自分泌机制促进癌细胞增殖。EGF转导各种信号，并在与细胞表面受体结合后最终刺激细胞增殖。阻止该肽与其受体的结合可能会带来肺癌治疗新方法的发展。几位研究者报告称，苏拉明对表达EGF受体（EGF-R）的癌细胞具有抗增殖活性，其作用方式是阻断配体与其受体的结合。在本研究中，我们使用两株表达EGF-R的肺癌细胞系（A549和PC-13）以及多种检测方法分析了苏拉明的抗肿瘤作用。受体结合检测证实A549和PC-13细胞具有EGF的细胞表面受体。苏拉明抑制了EGF与这些受体的结合。EGF和胎牛血清（FBS）刺激细胞增殖，但苏拉明以剂量依赖方式抑制了这些作用。在含有1%FBS的培养基中，200μg/ml的苏拉明分别使A549和PC-13细胞的生长降低了25%和15%。矛盾的是，抑制细胞增殖的苏拉明浓度低于有效抑制EGF与其受体结合的浓度。尽管当细胞受到EGF或FBS刺激时c-fos和c-myc mRNA的表达增加，但200μg/ml的苏拉明并未显著改变这种表达。苏拉明部分阻断了EGF诱导的细胞周期从G0/G1期向S期的进展。这些结果表明苏拉明部分阻断了EGF信号转导。苏拉明可能通过抑制核内酶以及部分阻断EGF信号转导来抑制细胞增殖。
