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在应用肝素及低分子量肝素(LMWH)防治肿瘤患者血栓栓塞性并发症时发现它们还具有显著的抗肿瘤活性,但其强大的抗凝活性成为抗肿瘤药物应用时的制约因素。对肝素进行化学修饰或将其与其他化合物偶联可获得抗凝活性低、抗肿瘤活性高的肝素衍生物。肝素衍生物的抗肿瘤机制有抑制类肝素酶活性、抑制P、L选择素介导的细胞间相互作用及抑制血管生长因子活性等。类肝素酶降解硫酸乙酰肝素(HS)侧链与肿瘤转移及肿瘤血管生成密切相关,P、L选择素介导的细胞间相互作用对肿瘤细胞的血源性转移过程有重要作用,血管生长因子所触发的血管生成是肿瘤生长、转移的必要条件。不同结构的肝素衍生物其抗肿瘤机制不完全相同。文章对抗肿瘤活性肝素衍生物的结构及其抗肿瘤机制作了综述。
In the application of heparin and low molecular weight heparin (LMWH) in the prevention and treatment of thromboembolic complications of tumor patients found that they also have significant antitumor activity, but its strong anticoagulant activity has become a limiting factor in the application of anti-tumor drugs. Chemical modification of heparin or its conjugation with other compounds yields heparin derivatives with low anticoagulant activity and high antitumor activity. The antitumor mechanism of heparin derivatives is inhibition of heparanase activity, inhibition of P, L-selectin-mediated cell-cell interactions and inhibition of vascular growth factor activity. Heparanase degrades the side chain of heparan sulfate (HS) and is closely related to tumor metastasis and tumor angiogenesis. P, L-selectin-mediated cell-cell interaction plays an important role in the hematogenous metastasis of tumor cells. Factors trigger angiogenesis is a necessary condition for tumor growth and metastasis. Different structures of heparin derivatives antitumor mechanism is not exactly the same. This review summarizes the structure of antitumor active heparin derivatives and their antitumor mechanisms.