Opposite angiogenic outcome of curcumin against ischemia and Lewis lung cancer models: in silico, in vitro and in vivo studies
Opposite angiogenic outcome of curcumin against ischemia and Lewis lung cancer models: in silico, in vitro and in vivo studies
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姜黄素对抗缺血和路易斯肺癌模型的相反血管生成结果：计算机、体外和体内研究
DOI：
10.1016/j.bbadis.2014.06.019
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发表时间：
2014-09-01
影响因子：
6.2
通讯作者：
Li, Xuejun
中科院分区：
文献类型：
--
作者：
Fan, Shengjun;Xu, Yan;Li, Xuejun
本研究的目的是探讨姜黄素对缺血和肺癌模型的血管生成作用。为了诱导缺血联合肺癌模型，将C57 BL/6小鼠的一侧股动脉断开，并将刘易斯肺癌（LLC）细胞异种移植到小鼠的另一侧。研究了姜黄素的血管生成作用及其相关机制。通过Western blot、双向凝胶电泳（2-DE）、计算机模拟和表面等离子体共振（SPR）技术检测分子靶点、信号级联和结合亲和力。姜黄素促进缺血后血液再循环，并通过相反地调节HIFAlpha/mTOR/VEGF/VEGFR级联反应抑制近交系C57 BL/6小鼠的肺癌进展。中性粒细胞弹性蛋白酶（NE）诱导的炎性刺激促进肺癌组织中的血管生成，但姜黄素通过直接减少NE的分泌并刺激α 1 -抗胰蛋白酶（α 1-AT）和胰岛素受体底物-1（IRS-1）的产生来逆转这些变化。同时，姜黄素剂量依赖性地影响内皮细胞（EC）管形成和鸡胚绒毛尿囊膜（CAM）新生血管。姜黄素对生理和病理性血管生成下的血管再生具有相反的作用，其通过负或正调节HIF 1 α/mTORNEGF/VEGFR级联来实现。姜黄素有望成为临床上同时治疗缺血性疾病和肺癌的一种新的治疗方式。(C)2014爱思唯尔有限公司版权所有。
The aim of this study was to investigate the angiogenic effects of curcumin on an ischemia and lung cancer model. To induce ischemia combined with lung cancer models, unilateral femoral arteries of C57BL/6 mice were disconnected on one side of the mouse and Lewis lung carcinoma (LLC) cells were xenografted on the opposite side. Angiogenic effects and underlying mechanisms associated with curcumin were investigated. Molecular target(s), signaling cascades and binding affinities were detected by Western blot, two-dimensional gel electrophoresis (2-DE), computer simulations and surface plasmon resonance (SPR) techniques. Curcumin promoted post-ischemic blood recirculation and suppressed lung cancer progression in inbred C57BL/6 mice via regulation of the HIFI alpha/mTOR/VEGF/VEGFR cascade oppositely. Inflammatory stimulation induced by neutrophil elastase (NE) promoted angiogenesis in lung cancer tissues, but these changes were reversed by curcumin through directly reducing NE secretion and stimulating alpha 1 -antitrypsin (alpha l-AT) and insulin receptor substrate-1 (IRS-1) production. Meanwhile, curcumin dose-dependently influenced endothelial cells (EC) tube formation and chicken embryo chorioallantoic membrane (CAM) neovascularization. Curcumin had opposite effects on blood vessel regeneration under physiological and pathological angiogenesis, which was effected through negative or positive regulation of the HIF1 alpha/mTORNEGF/VEGFR cascade. Curcumin had the promise as a new treatment modality for both ischemic conditions and lung cancer simultaneously in the clinic. (C) 2014 Elsevier B.V. All rights reserved.