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Evodiamine inhibits in vitro angiogenesis: Implication for antitumorgenicity.

机译:Evodiamine抑制体外血管生成:具有抗肿瘤作用。

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Evodiamine, the major bioactive compound isolated from Chinese herbal drug named Wu-Chu-Yu, has been reported to exhibit anti-tumor growth and metastasis. However, the effect of evodiamine on angiogenesis remains to be investigated. We used the fresh medium containing evodiamine or human lung adenocarcinoma cell (CL1 cells) derived conditioned media free of evodiamine to test their capability to induce in vitro angiogenesis, i.e., human umbilical vein endothelial cells (HUVECs) tube formation and invasion. We demonstrated that evodiamine could directly inhibit in vitro HUVECs tube formation and invasion. Locally administered evodiamine also inhibited the in vivo angiogenesis in the chick embryo chorioallantoic membrane (CAM) assay. The gene expression of vascular endothelial growth factor (VEGF) and the p44/p42 mitogen-activated protein kinase (MAPK, ERK) that correlated with endothelial cells angiogenesis were inhibited by evodiamine. We found that the evodiamine-treated CL1 cells derived conditioned medium showed decreased VEGF release and reduced ability of inducing in vitro tube formation. After the collection of conditioned media, the VEGF expression of remaining CL1 cells were determined by Western analyses and revealed that evodiamine decreased VEGF expression. Moreover, administration of recombinant human VEGF(165) (rhVEGF(165)) induced tube formation and ERK phosphorylation by HUVECs, and partially attenuated inhibitory effect of evodiamine. From these results, we suggested that evodiamine is a potent inhibitor of angiogenesis. The mechanism might involve at least the inhibition of VEGF expression, probably through repression of ERK phosphorylation.
机译:Evodiamine是从中草药Wu-Chu-Yu中分离出来的主要生物活性化合物,据报道具有抗肿瘤生长和转移作用。然而,依维他命对血管生成的作用尚待研究。我们使用了含有evodiamine的新鲜培养基或不含evodiamine的人肺腺癌细胞(CL1细胞)衍生的条件培养基来测试其诱导体外血管生成的能力,即人脐静脉内皮细胞(HUVECs)管的形成和侵袭。我们证明了依维他命可以直接抑制体外HUVECs管的形成和侵袭。在雏鸡胚胎绒膜尿囊膜(CAM)分析中,局部给予的依地洛明也抑制体内血管生成。 evodiamine抑制与内皮细胞血管生成相关的血管内皮生长因子(VEGF)和p44 / p42丝裂原活化蛋白激酶(MAPK,ERK)的基因表达。我们发现,用evodiamine处理的CL1细胞衍生的条件培养基显示出VEGF释放减少和诱导体外管形成的能力降低。收集条件培养基后,通过Western分析确定剩余CL1细胞的VEGF表达,并揭示依夫二胺降低了VEGF表达。此外,重组人VEGF(165)(rhVEGF(165))的施用诱导了HUVEC的管形成和ERK磷酸化,并部分减弱了依夫二胺的抑制作用。从这些结果,我们认为依维他命是血管生成的有效抑制剂。该机制可能至少通过抑制ERK磷酸化来抑制VEGF表达。

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