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中医药调控上皮-间质转化抑制肝癌转移的研究进展

王珏 张春蕾 汤凯悦 郑培永 宋海燕

引用本文:
Citation:

中医药调控上皮-间质转化抑制肝癌转移的研究进展

DOI: 10.3969/j.issn.1001-5256.2022.11.040
基金项目: 

上海市自然科学基金资助项目 20ZR1458900;

上海市青年科技英才扬帆计划项目 20YF1450000

利益冲突声明:所有作者均声明不存在利益冲突。
作者贡献声明:王珏负责资料分析及撰写论文;张春蕾和汤凯悦负责收集数据;郑培永、宋海燕负责拟定写作思路,修改论文并最后定稿。
详细信息
    通信作者:

    宋海燕, songhy@126.com

Research advances in traditional Chinese medicine in regulating epithelial-mesenchymal transformation to inhibit hepatocellular carcinoma metastasis

Research funding: 

Natural Science Foundation of Shanghai 20ZR1458900;

Sailing Plan of Shanghai for Young Scientific and Technological Talents 20YF1450000

More Information
    Corresponding author: SONG Haiyan, songhy@126.com(ORCID: 0000-0003-2155-8110)
  • 摘要: 转移是影响肝癌复发和死亡的主要原因,而上皮-间质转化(EMT)是肝癌转移的重要机制。EMT受TGFβ、Wnt/β-catenin、Notch等多种信号通路介导的转录因子Snail、Twist、ZEB等的调控。抑制肝癌EMT相关分子和信号通路是抑制肝癌侵袭转移的重要途径。近年来研究表明,多种中药复方或其有效成分具有抑制肝癌侵袭转移的作用,阻滞或逆转肝癌细胞EMT是其重要的作用机制。本文对EMT的作用和调控机制,以及近年来中药及其来源的天然化合物通过调控细胞EMT抑制肝癌侵袭转移的研究进行概述,以期为肝癌转移的中医药防治提供科学依据,为肝癌治疗提供新思路。

     

  • 图  1  肝癌细胞EMT调控的主要信号通路

    注:A,Wnt/β-catenin 信号通路;B, TGFβ/SMAD 信号通路;C, GF/RTK 信号通路; D, Jagged/Notch 信号通路; E, Hedgehog 信号通路; F, Hippo 信号通路;G, 低氧信号通路。

    Figure  1.  Major signaling pathways involved in the regulation of epithelial-mesenchymal transition in HCC cells

    表  1  中药复方调控EMT抑制HCC转移

    Table  1.   Chinese herbal compound regulates EMT to inhibit HCC metastasis

    中药复方 药物组成 作用及相关机制 参考文献
    鳖甲煎丸 醋鳖甲、射干、鼠妇、大黄、石韦、瞿麦、土鳖虫、蜂房、白芍、桃仁、牡丹皮、浙贝母、厚朴、人参、阿胶、桂枝、干姜、柴胡、黄芩、姜半夏 通过抑制NF-κB活化及snail表达或抑制GSK-3β磷酸化从而降低β-catenin活化水平,抑制EMT [22-23]
    健脾化瘀方 人参、白术、山药、茯苓、牡丹皮、丹参、郁金、莪术、柴胡、甘草 下调肝癌细胞Smad蛋白磷酸化水平和Snail表达,抑制EMT [25]
    扶正抗癌方 黄芪、灵芝、女贞子、莪术、水蛭、藤梨根、生牡蛎、丹参 抑制MMP,逆转TGFβ1诱导的肝癌细胞EMT [28]
    软坚护肝片 山豆根、夏枯草、虎杖、五味子、赤芍、三七等十味中药 抑制TGFβ1诱导的肝癌细胞EMT [30]
    松友饮 黄芪、丹参、枸杞、鳖甲、山楂 通过Akt/GSK-3β/β-catenin和TGFβ/Smad通路抑制EMT [32-33]
    下载: 导出CSV

    表  2  单味中药/组分调控EMT抑制HCC转移

    Table  2.   Single Chinese medicine/component regulates EMT to inhibit HCC metastasis

    组分 来源 作用及相关机制 参考文献
    山慈菇含药血清 山慈菇 抑制肝癌细胞EMT转化 [35]
    全蝎含药血清/水提物 全蝎 降低Snail表达,逆转肝癌细胞EMT [36]
    复方苦参提取液 苦参 抑制Wnt/β-catenin/c-Myc通路,逆转肝癌细胞EMT [37]
    银杏叶提取物 银杏叶 下调血小板活化因子,逆转肝癌细胞EMT [38]
    姜黄素 姜黄 逆转IL-6/STAT3通路,或减少UNC119蛋白表达而阻断Wnt/β-catenin、TGFβ通路以抑制肝癌细胞EMT [39-40]
    黄连素 黄连、黄柏 抑制TGFβ/ Smad通路,抑制肝癌细胞EMT [41]
    白花蛇舌草总黄酮 白花蛇舌草 逆转TGFβ1诱导肝癌细胞的EMT [42]
    裂果薯皂苷单体Ⅰ 裂果薯 阻断TGFβ/Smad信号通路介导的EMT [43]
    丹参酮ⅡA 丹参 调控TGFβ/Smad通路抑制肝癌细胞EMT [44]
    黄芪甲苷 黄芪 通过Akt/GSK-3β/β-catenin通路抑制EMT [45]
    蛇床子素 蛇床子 抑制EMT,下调MMP2和MMP9表达 [46]
    白藜芦醇 黎芦、虎杖、葡萄 上调miR-186-5p,下调Twist1表达,抑制EMT [47]
    异紫罗兰素 铁皮石斛 调控TGFβ/Smad和PI3K/Akt/mTOR通路,抑制肝癌细胞发生EMT [48]
    萝卜硫素 十字花科(板蓝根、大青叶、葶苈子、莱菔子等) 逆转TGFβ诱导的肝癌细胞EMT [49]
    下载: 导出CSV
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  • 收稿日期:  2022-03-28
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