Icariin exterts negative effects on human gastric cancer cell invasion and migration by vasodilator-stimulated phosphoprotein via Rac1 pathway
Icariin exterts negative effects on human gastric cancer cell invasion and migration by vasodilator-stimulated phosphoprotein via Rac1 pathway
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淫羊藿苷通过 Rac1 通路通过血管舒张刺激磷蛋白对人胃癌细胞侵袭和迁移产生负面影响
DOI：
10.1016/j.ejphar.2010.03.017
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发表时间：
2010-06-10
影响因子：
5
通讯作者：
Wei, Lei
中科院分区：
文献类型：
--
作者：
Wang, Yongping;Dong, Huimin;Wei, Lei
细胞运动主要由肌动蛋白依赖的细胞骨架调控，其中Rho GTPase rac1或血管扩张剂刺激的磷酸蛋白(Vasp)密切协作。本实验通过体外实验，探讨淫羊藿苷对人胃癌细胞株BGC-823侵袭和迁移的抑制作用及其分子机制。在50%的生长抑制浓度下，淫羊藿苷显著抑制肿瘤细胞的迁移和侵袭，其机制可追溯到rac1和Vasp的下调。与淫羊藿苷一起，针对rac1或Vasp的选定siRNA加强了这些抑制作用。Rac1依赖的siRNA下调Vasp的表达，而Vasp-siRNA导致Rac1的表达略有下降，这意味着Rac1的数量可能影响Vasp的表达水平。此外，转染了rac1基因的真核表达载体pcDNA3-EGFP-rac1-Q61L后，rac1基因和Vasp基因的表达水平均有所提高。这些结果表明淫羊藿苷通过依赖Rac1的Vasp途径对肿瘤细胞的侵袭和迁移产生负性影响，可能是一种潜在的抗癌药物。(C)2010年，爱思唯尔出版。
Cellular movement is mainly orchestrated by actin-dependent cytoskeleton in which Rho GTPase Rac1 or vasodilator-stimulated phosphoprotein (VASP) closely collaborates. In the present in vitro study, we investigated the inhibitory effect and underlying molecular mechanism of icariin, a pure extract of the traditional Chinese medicine Herba epimedii, on the invasive and migration properties of human gastric cancer cell line BGC-823. At 50% growth-inhibiting concentration, icariin significantly suppressed tumor cells migration and invasion, which were traceable to down-regulation of Rac1 and VASP. Together with icariin, the selected siRNA targeting Rac1 or VASP reinforced these inhibitory effects. Rac1-siRNA-dependent down-regulation of Rac1 led to a large drop in VASP expression, whereas VASP-siRNA led to a slight fall in Rac1 expression, implying that the amount of Rac1 may influence VASP expression level. Moreover, transfection with Rac1 plasmids pcDNA3-EGFP-Rac1-Q61L led to the enhancement in expression level of both Rac1 and VASP. These results indicate that icariin exerts negative effects on tumor cell invasion and migration via the Rac1-dependent VASP pathway and may be a potential anti-cancer drug. (C) 2010 Published by Elsevier B.V.