肝细胞生长因子抑制剂——NK4的抗肿瘤作用

肝细胞生长因子(hepatocyte growth factor, HGF)是一种多功能的细胞因子，其生物学活性由c-Met蛋白所介导.HGF/c-Met信号通路在肿瘤生成、侵袭、转移以及肿瘤新生血管生成方面起重要促进作用. 因此, HGF/c-Met信号转导通路可以作为抗肿瘤药物设计的靶点.其中，HGF-α链N端447个氨基酸组成的NK4蛋白是HGF的特异性拮抗剂，它不仅通过抑制HGF/c-Met系统的信号转导发挥抗肿瘤效应；而且可以通过拮抗HGF和其它血管生成因子如成纤维细胞生长因子（fibroblast growth factors, FGF)、血管内皮生长因子（vascular endothelial growth factor, VEGF）的活性，进而抑制肿瘤新生血管生成，最终导致肿瘤细胞的凋亡.NK4的这种双重抗肿瘤功能使其成为一类很有前景的新型抗肿瘤药物.本文就NK4对肿瘤的抑制作用及其机制的研究进展进行综述.

NK4 with Anti-tumor Activity: A Competitive Antagonist against HGF

Hepatocyte growth factor (HGF) is a multifunctional cytokine to bind c-Met receptor. HGF/c-Met signaling plays an important role in tumorigenesis, tumor invasion, metastasis and angiogenesis. Thus, HGF/c-Met was proposed as a target for anti-tumor drug design. As a competitive antagonist against HGF, NK4 consists of 447 amino acids which are identical to the N-terminal of HGFα chain. NK4 inhibits tumor angiogenesis induced by vascular endothelial cell growth factor and basic fibroblast growth factor to promote the apoptosis of tumor cells. Here, we reviewed the anti-tumor effect of NK4 and the investigation of the underlying mechanisms.