人内皮抑素部分序列——Es-2的生物活性研究

Biological activity of human endostatin-derived synthetic peptide——Es-2

目的:检测人工合成多肽Es-2抑制血管生成活性及其对肿瘤生长的影响。方法:采用MTT法和鸡胚给药实验,观察Es-2对肿瘤细胞和鸡胚尿囊绒膜(CAM)上血管生成的抑制情况。建立C57BL/6黑色素瘤(B16F10)小鼠模型,以不同剂量皮下注射给药,测量各组小鼠皮下移植肿瘤体积变化和抑瘤率。结果:Es-2对肿瘤细胞无抑制现象;在CAM实验中,新生血管生长受到明显的抑制。C57BL/6小鼠给药10 d后治疗组与对照组相比,Es-2 20 mg/kg组对小鼠黑色素瘤生长有一定抑制作用,其效果相当于10 mg/kg内皮抑素的治疗效果(P<0.05)。结论:Es-2具有开发成抗肿瘤药物的前景。

Aim： Synthetic peptides corresponding to the sequences 60 - 70 （Es-2） of human endostatin have been found to inhibit basic fibroblast growth factor-induced directional migration and tubular morphogenesis of microvascular endothelial cells. Accordingly, the peptide induced the loss of focal adhesions and actin stress fibers in these cells. In this study, we aimed to investigate the effects of endostatin-derived peptide Es-2 on angiogenesis and the growth of tumor in vivo. Methods： A peptide of 25 amino acids including the sequences 60 - 70 of endostatin was synthesized, MTF and chick chorioallantoic membrane （CAM）assay was conducted. A treatment of mice bearing B16F10 melanoma with Es-2 was also carried out. Results： In CAM, Es-2 was found to be fully biologically active in the angiogenesis assays and it even showed greater potency and efficacy than full-length human endostatin. Compared with the negative control group, Es-2 could significantly reduce the growth of melanoma in vivo （ P 〈 0.05 ）. Conclusion： Synthetic peptide Es-2 has the promising in the application of clinical therapy.