Wu Lian-Qiu, Ouyang Xue-Yu, Liu Yang, Peng Shan-Ying, Wang Lin, Wang Wen-Jie
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
J Asian Nat Prod Res. 2011 Oct;13(11):984-92. doi: 10.1080/10286020.2011.603696. Epub 2011 Oct 10.
SY0916 is a novel platelet-activating factor receptor antagonist. The objective of this study is to explore the anti-angiogenesis effects of SY0916 on human umbilical vascular endothelial cell (HUVEC) and to understand its possible mechanism. The effect of SY0916 on proliferation of HUVEC was measured by the MTT method, whereas the effect of SY0916 on HUVEC chemotaxis was carried out by Boyden chamber assay. The activities of metalloproteinase (MMP)-9 and MMP-2 were detected using gelatin zymography, and the expression of intercellular adhesion molecules-1 (ICAM-1) was measured by Western blot analysis. The 2D tube formation experiment of HUVEC with 10% fetal calf serum on Matrigel was also evaluated. It was shown that SY0916 had significant inhibitory effects on the proliferation and the chemotaxis of HUVEC induced by phorbol-12-myristate-13-acetate in a positive dose-dependent manner. Furthermore, SY0916 could significantly suppress the activity of MMP-2 and MMP-9 and decrease the expression of ICAM-1 in HUVEC. In 2D tube formation test, SY0916 could effectively inhibit the formation of vascular structure on Matrigel. The results showed that SY0916 could block the chemotaxis of HUVEC, and then inhibit the tube formation on Matrigel. Such anti-angiogenesis effect of SY0916 on HUVEC might relate to downregulate the expressions of MMP-2, MMP-9, and ICAM-1.
SY0916是一种新型血小板活化因子受体拮抗剂。本研究的目的是探讨SY0916对人脐静脉血管内皮细胞（HUVEC）的抗血管生成作用，并了解其可能的机制。采用MTT法检测SY0916对HUVEC增殖的影响，采用Boyden小室试验检测SY0916对HUVEC趋化性的影响。用明胶酶谱法检测金属蛋白酶（MMP）-9和MMP-2的活性，用蛋白质免疫印迹分析检测细胞间黏附分子-1（ICAM-1）的表达。还评估了HUVEC在Matrigel上添加10%胎牛血清的二维管形成实验。结果表明，SY0916对佛波醇-12-肉豆蔻酸酯-13-乙酸酯诱导的HUVEC增殖和趋化性具有显著的抑制作用，且呈正剂量依赖性。此外，SY0916可显著抑制HUVEC中MMP-2和MMP-9的活性，并降低ICAM-1的表达。在二维管形成试验中，SY0916可有效抑制Matrigel上血管结构的形成。结果表明，SY0916可阻断HUVEC的趋化性，进而抑制Matrigel上的管形成。SY0916对HUVEC的这种抗血管生成作用可能与下调MMP-2、MMP-9和ICAM-1的表达有关。
