内皮抑制素抑制TNFα和IL-8介导的血管内皮细胞增殖及其表面粘附分子的表达

Endostatin Inhibits Proliferation of Vascular Endothelial Cells Mediated by TNFαand IL-8 and Down-regulates Expression of Adhesive Molecules

目的：探讨重组人内皮抑制素对 ＴＮＦα和ＩＬ－８介导的人血管内皮细胞株（ｅｎｄｏｔｈｅｌｉａｌ ｃｅｌｌ ｏｆ ｖｅｓｓｅｌｓ，ＥＣＶ）细胞增殖的抑制作用，并观察内皮抑制素对ＥＣＶ表面粘附分子表达的影响。方法：用ＭＴＴ法测定ＥＣＶ的增殖；用间接免疫荧光法，在流式细胞仪上测定 ＥＣＶ表面粘附分子的表达。结果：内皮抑制素浓度在 １００～１００００ ｎｇ／ｍｌ时，能显著抑制ＥＣＶ的增殖（Ｐ＜０．０１），并抑制ＩＬ－８和ＴＮＦα介导的ＥＣＶ增殖，且呈剂量依赖性关系。内皮抑制素在 １００～１０００ ｎｇ／ｍｌ时可抑制内皮细胞表面ＣＤ６２Ｅ、ＣＤ４０等粘附分子的表达。结论：内皮抑制素不但可抑制血管内皮细胞的增殖，控制肿瘤新生血管的形成，而且可抑制血管内皮细胞表面粘附分子的表达，对肿瘤的转移亦可能起抑制作用。

Objectives: The current study was designed to investigate the inhibitive effect of recombinant human endostatin on the proliferation of human endothelial cells of vessels (ECV) mediated by TNFα and IL-8. The influence of endostatin on the expression of adhesive molecules on the surface of ECV was also studied. Methods: The effect of endostatin on the proliferation of ECV in vitro was examined using MTT assay. The expression of adhesive molecules on the surface of ECV was determined by flow cytometry. Results: The proliferation of ECV was inhibited significantly after ECV was incubated with 100 - 10 000 ng/ml of endostatin for 72h. The stimulating effect of TNFα and IL-8 on ECV was also suppressed markedly by endostatin. A dose-dependent inhibition was observed. At the level of 100 - 1000 ng/ml, endostatin also inhibited significantly the expression of CD62E and CD40 on the surface Of ECV. Conclusions: Endostatin not only exerts an inhibitive effect on the proliferation of endothelial cells, which may be helpful to the control of angiogenesis in solid tumors, but also suppresses the expression of adhesive molecules on the surface of endothelial cells. Thus, endostatin maybe play an important role in dealing with the metastasis of solid tumor.