Pesenti E, Sola F, Mongelli N, Grandi M, Spreafico F
Farmitalia Carlo Erba Research Center, R&D/Oncology Lab., Milan, Italy.
Br J Cancer. 1992 Aug;66(2):367-72. doi: 10.1038/bjc.1992.272.
Inhibition of angiogenesis through blocking of growth factors involved in this process could be a novel therapeutic approach in several important pathologies, neoplasia among them. Suramin has recently been described to possess antineoplastic activity in animals and humans, and it has been proposed that an important role in this activity is played by antagonism of growth factors and especially bFGF. To investigate this hypothesis in vivo, we used gelatin sponges loaded with bFGF and implanted subcutaneously in mice. Suramin showed an inhibitory activity on bFGF-induced angiogenesis, whereas it was inactive in the case of heparin-complexed bFGF. Suramin was also studied in an in vivo model of tumour-induced angiogenesis using the murine M5076 reticulosarcoma, a tumour producing significant levels of bFGF. Suramin was able to reduce tumour growth and tumour induced angiogenesis, and exogenous administration of bFGF countered suramin effects.
通过阻断参与这一过程的生长因子来抑制血管生成,可能是几种重要病症(包括肿瘤形成)的一种新型治疗方法。最近有报道称,苏拉明在动物和人类中具有抗肿瘤活性,并且有人提出,生长因子尤其是碱性成纤维细胞生长因子(bFGF)的拮抗作用在这种活性中发挥着重要作用。为了在体内研究这一假说,我们使用负载bFGF的明胶海绵并将其皮下植入小鼠体内。苏拉明对bFGF诱导的血管生成具有抑制活性,而在肝素复合bFGF的情况下则无活性。我们还使用产生大量bFGF的鼠M5076网状肉瘤,在肿瘤诱导血管生成的体内模型中研究了苏拉明。苏拉明能够减少肿瘤生长和肿瘤诱导的血管生成,并且外源性给予bFGF可抵消苏拉明的作用。