State Key Laboratory of Microbial Technology, Shandong University, Jinan 250100, China.
Biotechnol Lett. 2010 Nov;32(11):1609-13. doi: 10.1007/s10529-010-0342-5. Epub 2010 Jul 6.
Angiogenesis is important in tumor development. Vascular endothelial growth factor (VEGF) is involved in this process. In this report, we constructed a recombinant protein (called FK) by fusing the second immunoglobulin-like (Ig-like) domain of a human fms-like tyrosine kinase (Flt-1) with the third Ig-like domain of human kinase insert domain-containing receptor (KDR). FK bound to VEGF(165) in a dose-dependent manner with a disocciation constant (Kd) of 2.7 pM. In addition, FK specifically inhibited the proliferation of human microvascular endothelial cell (HMEC) and human umbilical vein endothelial Cell (HUVEC) stimulated by VEGF(165). Subsequent studies also demonstrate that FK efficaciously suppresses growth of a variety of tumors, which could make FK a potential drug candidate in anti-tumor therapy.
血管生成在肿瘤的发展过程中很重要。血管内皮生长因子（VEGF）参与了这一过程。在本报告中，我们通过融合人源 fms 样酪氨酸激酶（Flt-1）的第二个免疫球蛋白样（Ig 样）结构域与人源激酶插入结构域受体（KDR）的第三个 Ig 样结构域，构建了一种重组蛋白（称为 FK）。FK 以剂量依赖的方式与 VEGF（165）结合，解离常数（Kd）为 2.7 pM。此外，FK 特异性抑制了 VEGF（165）刺激的人微血管内皮细胞（HMEC）和人脐静脉内皮细胞（HUVEC）的增殖。随后的研究还表明，FK 能有效地抑制多种肿瘤的生长，这使得 FK 成为抗肿瘤治疗的一种有潜力的候选药物。
