摘要
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。
Heparin and low molecular heparin （LMWH） were found to have effective anti-neoplastic activity when they are used for the prevention and treatment of thromboembolic complications. However, when heparin and LMWH are used as anticaneer drugs, their utility will be limited because of their strong anticoagulant properties. Through chemical modification or couple with other com- pounds, heparin derivates with lowered anticoagulant activity and elevated anti-neoplastic activity can be obtained. Antineoplastic mechanisms of the heparin derivates include inhibition of heparanase activity, inhibition of cell-cell interaction mediated by P, L-selectins,inhibition of vascular growth factor and so on. The heparanase which is capble of cleaning heparan sulfate （HS） side chains correlates with tumor metastasis and angiogenesis. The cell-cell interaction mediated by P, L-seleetins is important on hema- togenous metastasis of cancer. Angiogenesis activated by angiogenesis factor is the basis of growth and metastasis of tumor. The anti- neoplastic mechanisms of different heparin derivates vary owing to their distinct structures. The structures and mechanisms of heparin derivates are reviewed.
出处
《药物生物技术》
CAS
2013年第3期266-270,共5页
Pharmaceutical Biotechnology
关键词
肝素衍生物
化学修饰
抗肿瘤机制
Heparin derivates, Chemical modification, Anti-neoplastic mechanisms
作者简介
刘子铭（1987-），男，山东潍坊人，在读硕士研究生，主要研究方向：微生物与生化药学，sdaqlzm@163．com。
通讯作者：崔慧斐，女，教授，硕士生导师，0531-88380288，euihuifei@sdu．edu．cn。
