以整合素αvβ3为靶点的RGD配体在抗肿瘤血管新生中的应用

整合素αvβ3是一种能特异性识别RGD序列的膜受体蛋白，其与含RGD（Arg-Gly-Asp）模体的蛋白质结合的特异性在肿瘤细胞的粘附、迁移、浸润及肿瘤血管新生中起重要作用.由于整合素αvβ3在多种肿瘤细胞表面高表达而在正常细胞中低表达或不表达，因此其成为肿瘤治疗的理想靶点.肿瘤新生血管为肿瘤的生长提供营养，因此近年来抑制肿瘤血管新生也成为肿瘤治疗的重要途径.有研究显示，几种RGD毒素蛋白不但以整合素αvβ3为靶点靶向结合到肿瘤部位从而具有直接抗肿瘤细胞增殖、黏附、迁移及浸润功能，而且它们还具有抗肿瘤血管新生的作用，因此RGD毒素蛋白可从上述两方面抑制肿瘤生长与转移.本文就整合素αvβ3为靶向的RGD配体结构特点及其在肿瘤治疗中的靶向治疗和抗血管新生应用及前景加以综述.

Application of RGD ligands targeting Integrin αvβ3 in anti-tumor Angiogenesis

Integrin αvβ3 is one kind of membrane receptor protein that specifically recognizes the RGD (Arg-Gly-Asp) motif. This nature of specially binding to the RGD motif proteins plays an important role in tumor cells adhesion, migration, invasion and tumor angiogenesis. Integrin αvβ3 is highly expressed in the tumor cells but it is found in relatively low expression levels in normal cells, so αvβ3 becomes an ideal target for tumor therapy. Angiogenesis provides nutrition for the growth of the tumor, so tumor angiogenesis inhibition has also become an important way in tumor therapy in the recent years. RGD toxin proteins not only have the abilities of inhibiting tumor cell proliferation, adhesion, migration and invasion by targeting integrin αvβ3 when bound to the tumor cells, but also have the function for tumor angiogenesis inhibition. Thus, RGD toxin proteins can inhibit tumor growth and metastasis based on the above two ways. In this article, the structural features of RGD ligands targeting integrin αvβ3 and application will be reviewed, the prospects in the tumor therapy will also be mentioned.