Anti-angiogenesis effect of trichosanthin and the underlying mechanism
Anti-angiogenesis effect of trichosanthin and the underlying mechanism
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天花粉素的抗血管生成作用及其机制
DOI：
10.1016/j.bbrc.2012.11.080
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发表时间：
2013-01-11
影响因子：
3.1
通讯作者：
Ma, Xin
中科院分区：
文献类型：
--
作者：
He, Dongxu;Jin, Jian;Ma, Xin
肿瘤的生长和转移依赖于血管生成。肿瘤血管生成是由肿瘤细胞分泌的生长因子引发的;然后在预先存在的血管中触发下游信号，以产生新的血管网络。天花粉蛋白（TCS）是一种I型核糖体失活蛋白，具有抗肿瘤活性，但其潜在机制尚不清楚。在这项研究中，我们发现，无毒剂量的TCS减少伤口愈合和迁移的H5 V小鼠心脏毛细血管内皮细胞（ECs）诱导的人绒毛膜癌（HCM）细胞，以及JAR诱导的大鼠三级肠系膜动脉血管生成。TCS对肿瘤细胞和EC/动脉均有效。首先，TCS减少血管内皮细胞的血管内皮生长因子的转录和分泌。第二，TCS因此抑制肿瘤细胞诱导的、细胞外信号调节激酶介导的内皮细胞和血管中的血管生成信号。总之，TCS抑制肿瘤血管生成的能力有助于其抗肿瘤活性。(C)2012 Elsevier Inc. All rights reserved.
The growth and metastasis of tumors depend on angiogenesis. Tumor angiogenesis is initiated by the secretion of growth factors from tumor cells; downstream signals are then triggered in pre-existing blood vessels to sprout a new vascular network. Trichosanthin (TCS) is a type I ribosome-inactivating protein that has anti-tumor activity, but the underlying mechanism remains unclear. In this study, we found that a non-toxic dose of TCS decreased the wound-healing and the migration of H5V mouse heart capillary endothelial cells (ECs) induced by human choriocarcinoma (JAR) cells, as well as the JAR-induced angiogenesis of rat third-order mesenteric arteries. TCS was effective on both tumor cells and ECs/arteries. First, TCS decreased vascular endothelial growth factor transcription and secretion by JAR cells. Second, TCS consequently inhibited the tumor cell-induced, extracellular signal-regulated kinase-mediated angiogenic signal in ECs and blood vessels. In conclusion, the ability of TCS to inhibit tumor angiogenesis contributes to its anti-tumor activity. (C) 2012 Elsevier Inc. All rights reserved.