Sandgren Staffan, Belting Mattias
Department of Cell and Molecular Biology, Biomedical Centre C-13, Lund University, SE-221 84 Lund, Sweden.
Anticancer Res. 2003 Mar-Apr;23(2B):1223-8.
Polyamines are necessary for tumour cell growth. Inhibition of endogenous polyamine biosynthesis results in compensatory up-regulation of polyamine uptake. Here, the combined effect of suramin and the polyamine biosynthesis inhibitor alpha-difluoromethylornithine (DFMO) on human carcinoma cell proliferation was studied. Suramin selectively inhibited the growth of tumour cells made dependent on extracellular polyamines by DFMO-treatment. In an animal tumour model, low non-toxic doses of suramin resulted in a 2-fold increase in DFMO tumour growth reduction. Moreover, suramin bound strongly to polyamine-agarose and significantly inhibited polyamine uptake in DFMO-treated cells. Our results indicate that non-toxic doses of suramin augment tumour growth inhibition by DFMO, and that a combination of these well-studied anticancer drugs may represent an additional strategy for cancer treatment.
多胺是肿瘤细胞生长所必需的。抑制内源性多胺生物合成会导致多胺摄取的代偿性上调。在此，研究了苏拉明与多胺生物合成抑制剂α-二氟甲基鸟氨酸（DFMO）对人癌细胞增殖的联合作用。苏拉明选择性抑制经DFMO处理而依赖细胞外多胺的肿瘤细胞生长。在动物肿瘤模型中，低无毒剂量的苏拉明使DFMO对肿瘤生长的抑制作用增加了两倍。此外，苏拉明与多胺琼脂糖强烈结合，并显著抑制DFMO处理细胞中的多胺摄取。我们的结果表明，无毒剂量的苏拉明增强了DFMO对肿瘤生长的抑制作用，并且这两种经过充分研究的抗癌药物的联合使用可能代表了一种额外的癌症治疗策略。
