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恶性肿瘤一直以来都是全球范围内的热门课题,肿瘤细胞的恶性转移是肿瘤致死率居高不下的重要原因。研究发现,肝素酶(Heparanase,HPA)在肿瘤发展的过程中起关键作用,是抗肿瘤治疗的重要靶点;肝素酶抑制剂,通过降低HPA的活性或抑制HPA的表达,有效抑制肿瘤细胞的侵袭和迁移,是颇具潜力的抗肿瘤治疗药物。文章对HPA作为肿瘤治疗靶点以及针对该靶点的抗肿瘤新药研发进行了综述,重点介绍了具有干扰HPA活性的底物类似物——肝素衍生物SST0001和硫酸化寡糖PG545、小分子化合物,以及抑制HPA表达的小干扰RNA(siRNA)等,为设计合理、高效的肝素酶抑制剂提供参考。
Malignant tumors have always been a hot topic in the world. The malignant metastasis of tumor cells is an important reason for the high tumor lethality. Heparanase (HPA) plays a key role in the development of tumors and is an important target of anti-tumor therapy. Heparinase inhibitors effectively inhibit tumors by decreasing the activity of HPA or inhibiting the expression of HPA Cell invasion and migration, is a potential anti-tumor drug. In this review, we reviewed the development of HPA as a tumor therapeutic target and the development of new anti-tumor drugs targeting this target. We focused on the studies of HPA-stimulated substrate analogues heparin derivatives SST0001 and sulfated oligosaccharides PG545, small molecule compounds , As well as small interfering RNA (siRNA) inhibiting the expression of HPA, provide a reference for the design of a reasonable and efficient heparanase inhibitor.