A new epigallocatechin gallate derivative isolated from Anhua dark tea sensitizes the chemosensitivity of gefitinib via the suppression of PI3K/mTOR and epithelial-mesenchymal transition
A new epigallocatechin gallate derivative isolated from Anhua dark tea sensitizes the chemosensitivity of gefitinib via the suppression of PI3K/mTOR and epithelial-mesenchymal transition
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从安化黑茶中分离出的一种新的表没食子儿茶素没食子酸酯衍生物通过抑制 PI3K/mTOR 和上皮间质转化来增敏吉非替尼的化疗敏感性
DOI：
10.1016/j.fitote.2020.104590
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发表时间：
2020
期刊：
影响因子：
3.4
通讯作者：
Yanhua Fan
中科院分区：
文献类型：
--
作者：
Jianyu Liu;Ting Zhong;Ping Yi;Chengcheng Fan;Zhen Zhang;Guangyan Liang;Yongnan Xu;Yanhua Fan
吉非替尼的获得性耐药限制了其临床应用。已发现表没食子儿茶素-3-没食子酸酯（EGCG）增强吉非替尼对抗耐药的功效。然而，NSCLC的细胞和分子机制尚未完全阐明。本研究从安化黑茶中分离并鉴定了一个新的表没食子儿茶素没食子酸酯衍生物（2 R，3R-6-甲氧基羰基没食子儿茶素3-O-没食子酸酯，以下简称EGCGD）（1）和三个已知的表没食子儿茶素没食子酸酯化合物表儿茶素3-O-没食子酸酯（2）、没食子儿茶素3-O-没食子酸酯（3）和表没食子儿茶素-3-O-没食子酸酯（4，EGCG）。药理学研究表明，EGCGD对吉非替尼耐药的HCC 827-Gef细胞的抗肿瘤活性优于包括EGCG在内的其他3种表没食子儿茶素没食子酸酯化合物，表明在EGCG中引入6-甲氧羰基可能会增强其抗肿瘤活性。进一步的分子机制研究表明EGCGD通过抑制上皮-间充质转化（EMT）和双重抑制PI 3 K/mTOR来增强吉非替尼对HCC 827-Gef细胞的杀伤作用。
The acquired resistance to gefitinib limits its clinical application. Epigallocatechin-3-gallate (EGCG) has been found to enhance the efficacy of gefitinib against resistant. However, the cellular and molecular mechanisms have not been completely illuminated in NSCLC. In this study, a new epigallocatechin gallate derivative (2R,3R-6-methoxycarbonylgallocatechin 3-O-gallate, the following referred to as EGCGD) (1) and three known epigallocatechin gallate compounds including epicatechin 3-O-gallate (2), gallocatechin 3-O-gallate (3) and epigallocatechin-3-O-gallate (4, EGCG) were isolated and identified from Anhua dark tea. The pharmacological studies showed EGCGD was more effective against gefitinib-resistant HCC827-Gef cells compared to that of other three epigallocatechin gallate compounds including EGCG, suggesting that introduction of 6-methoxycarbonyl to EGCG might enhance its antitumor activities. Further study on molecular mechanism showed EGCGD increased the potency of gefitinib against HCC827-Gef cells via suppression of epithelial-Mesenchymal transition (EMT) and dual inhibition of PI3K/mTOR.