Epicatechin-3-gallate reverses TGF-β1-induced epithelial-to-mesenchymal transition and inhibits cell invasion and protease activities in human lung cancer cells
Epicatechin-3-gallate reverses TGF-β1-induced epithelial-to-mesenchymal transition and inhibits cell invasion and protease activities in human lung cancer cells
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DOI：
10.1016/j.fct.2016.05.009
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发表时间：
2016-08-01
影响因子：
4.3
通讯作者：
Chen, Pei-Ni
中科院分区：
文献类型：
--
作者：
Huang, Shu-Fang;Horng, Chi-Ting;Chen, Pei-Ni
上皮-间质转化（Epithelial-to-mesenchymal transition， EMT）和侵袭潜能被认为是肿瘤转移的重要因素，是癌症死亡的主要原因。EMT是一个多步骤的过程，包括增益入侵、细胞骨架改变、细胞粘附和蛋白水解细胞外基质降解。表儿茶素-3-没食子酸酯（ECG）是绿茶中的一种天然多酚成分，具有多种抗氧化和抗炎作用。然而，心电图对肺癌侵袭及EMT的影响尚不清楚。我们提供了支持ECG抗转移作用的分子证据。该化合物通过降低基质金属蛋白酶-2 （P < 0.001）和尿激酶型纤溶酶原激活物（P < 0.001）的活性来抑制高转移性A549细胞的侵袭（P < 0.001）。ECG还逆转了转化生长因子(TGF)- β 1诱导的EMT和上调上皮标志物，如E-cadherin。相反，ECG抑制间充质标志物，如纤维连接蛋白和p-FAR。皮下接种该化合物也能抑制体内A549细胞的肿瘤生长。因此，心电图可作为一种抗癌和抗侵袭剂，用于人肺癌细胞的辅助治疗和转移控制。心电图也可以作为一种有效的化学预防剂来预防tgf - β 1诱导的EMT。(C) 2016 Elsevier Ltd.版权所有。
Epithelial-to-mesenchymal transition (EMT) and invasion potential have been considered as essential factors in cancer metastasis, which is the major cause of cancer death. EMT is a multi-step process that involves gain invasion, cytoskeleton change, cell adhesion, and proteolytic extracellular matrix degradation. Epicatechin-3-gallate (ECG), which is a natural polyphenolic component of green tea, elicits several antioxidant and anti-inflammatory effects. However, the effects of ECG on cancer invasion and EMT of human lung carcinoma remain unknown. We provided molecular evidence supporting the anti metastatic effect of ECG. This compound suppressed the invasion (P < 0.001) of highly metastatic A549 cells by reducing the activities of matrix metalloproteinase-2 (P < 0.001) and urokinasetype plasminogen activator (P < 0.001). ECG also reversed the transforming growth factor (TGF)-beta 1-induced EMT and upregulated epithelial markers, such as E-cadherin. Conversely, ECG inhibited mesenchymal markers, such as fibronectin and p-FAR. The subcutaneous inoculation of this compound also inhibited the tumor growth of the A549 cells in vivo. Therefore, ECG may be used as an anti-cancer and anti invasion agent for the adjuvant treatment and metastasis control of human lung cancer cells. ECG may also be administered as an effective chemopreventive agent against TGF-beta 1-induced EMT. (C) 2016 Elsevier Ltd. All rights reserved.