Inhibition of endothelial cell proliferation, in vitro angiogenesis, and the down-regulation of cell adhesion-related genes by genistein - Combined with a cDNA microarray analysis
Inhibition of endothelial cell proliferation, in vitro angiogenesis, and the down-regulation of cell adhesion-related genes by genistein - Combined with a cDNA microarray analysis
复制标题
DOI：
10.1080/10623320600903940
复制
发表时间：
2006-07-01
影响因子：
--
通讯作者：
Tokunaga, Osamu
中科院分区：
文献类型：
--
作者：
Piao, Meihua;Mori, Daisuke;Tokunaga, Osamu
抗血管生成是目前治疗癌症的有效策略之一，内皮细胞在血管生成过程中起着关键作用。染料木素是一种酪氨酸激酶抑制剂，是大豆中丰富的主要异黄酮，已知可抑制肿瘤生长和血管生成。然而，染料木素影响内皮细胞的确切分子机制尚未阐明。本研究采用cDNA芯片技术研究了10 μ M染料木素对人脐静脉内皮细胞（HUVECs）的靶向基因影响。结果，共有256个基因的表达改变了两倍以上。其中包括与细胞增殖、粘附、转录、翻译、代谢、细胞骨架、凋亡、激酶和功能未知相关的基因。逆转录聚合酶链式反应（RT-PCR）或免疫荧光染色证实细胞粘附相关基因VE-cadherin、间隙连接蛋白α 1 （connexin 43）、整合素α V和多聚蛋白mRNA或蛋白表达下调。电镜观察染料木素对细胞粘附的影响。此外，通过倒置显微镜和电镜观察证实染料木素在基质上的抗血管生成作用。综上所述，染料木素在体外作为内皮细胞增殖和血管生成的负介质，部分通过下调细胞粘附相关基因和损害细胞粘附来影响内皮细胞。
Antiangiogenesis is presently one of the powerful strategies for treating cancer, and endothelial cells play a pivotal role in the process of angiogenesis. Genistein, a tyrosine kinase inhibitor, a major isoflavone plentiful in soybeans, is known to inhibit both tumor growth and angiogenesis. However, the precise molecular mechanism( s) by which genistein affects endothelial cells has yet to be elucidated. In the present study, a cDNA microarray was performed to investigate the targeted genes of human umbilical vein endothelial cells (HUVECs) affected by 10 mu M genistein. As a result, a total of 256 genes showed an altered expression of more than twofold. Among them were the genes related to cell proliferation, adhesion, transcription, translation, metabolism, cytoskeleton, apoptosis, kinases, and functionally unknown. The down-regulation of mRNA or the protein expression of cell adhesion - related genes, including VE-cadherin, gap junction protein alpha 1 ( connexin 43), integrin alpha V, and multimerin, were confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) or by immunofluorescence staining. The impaired cell-cell adhesion by genistein was also observed by electron microscopy. In addition, the antiangiogenesis role of genistein was confirmed on Matrigel using inverted microscopy and electron microscopy. In conclusion, genistein affects endothelial cells as a negative mediator of proliferation and angiogenesis in vitro, partially by down-regulating cell adhesion - related genes and impairing cell adhesions.