Endostar对肿瘤血管内皮细胞生长及功能的抑制作用

Endostar inhibits proliferation and cell functions of tumor-derived endothelial cells

目的探讨Endostar对肿瘤血管内皮细胞生长和功能的抑制作用及其相关的抗血管形成机制。方法采用A549细胞上清诱导人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVEC)成为肿瘤血管内皮细胞(tumor-derived endothelial cells,Td-EC),通过MTT法、细胞迁徙试验、流式细胞术、TUNEL法等检测Endostar对Td-EC细胞生物学特性的影响。结果Endostar在体外对于Td-EC有显著的生长抑制作用,并具有时间和浓度依赖性,但对于HUVEC的生长抑制作用并不显著;一定浓度的Endostar能显著降低Td-EC细胞迁徙活性,促使细胞凋亡数目增加、细胞形态学发生改变,并能显著增加Td-ECS期细胞比例(P<0.01),而同样条件下,Endostar影响细胞迁徙活性及促进细胞凋亡的作用对于HUVEC并不显著(P>0.05)。结论Endostar可以特异性地抑制肿瘤血管内皮细胞的生长及功能。

Objective Tumor vessels were foundation of tumors＇formation,growth and metastasis,and the destruction of a spot of them would lead to wide avascular necrosis of tumor cells,so the specific killing effect on tumor vasculature endothelial cells had become one of the most important strategies for tumor therapy. Endostar,a novel recombinant human endostatin expressed and purified with an additional nine-amino acid sequence,is a new anti-drug. This study aimed to determine how endostar to affect the behavior of endothelial cells and tumor endothelial cells in vitro and in vivo. Methods Human umbilical vein endothelial cells （ HUVEC） was isolated and cultured followed by identification with Ⅷ factor related antigens. The cells differentiated into tumor-derived endothelial cells （ Td-ECs） by co-culturing with supernatants of A549 cells. The anti-effect of endostar on Td-ECs was detected with MTT assay,cell migration assay,flow cytometry and TUNEL assay. Results Endostar had a significant effect on the proliferation of Td-EC in a time-and concentration-dependent manner. At the same time,though Endostar at a certain concentration inhibited cell migration process significantly,arrested the cells at G0 /G1 and S phases and induced cell apoptosis （ P〈0. 01） ,however, under the same conditions,Endostar had little impact on HUVEC （ P〉0. 05） . Conclusion Our study indicates a novel function of endostar,to inhibit and Td-ECs proliferation in vitro. So,using endostar for cancer therapy is worthwhile for further study in clinical trials.