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

doi:10.3969/j.issn.1001-5256.2022.11.040

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

a.
上海中医药大学附属龙华医院脾胃病研究所, 上海 200032
b.
上海中医药大学附属龙华医院急诊科, 上海 200032

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

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出版历程
- 收稿日期: 2022-03-28
- 录用日期: 2022-04-30
- 出版日期: 2022-11-20

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

a.
Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
b.
Department of Emergency, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China

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

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。
- 肝肿瘤 /
- 肿瘤转移 /
- 上皮-间质转化 /
- 中草药
Abstract: Metastasis is an important factor for the high recurrence and mortality rates of hepatocellular carcinoma (HCC), and epithelial-mesenchymal transition (EMT) is an important mechanism of HCC metastasis. EMT is regulated by the transcription factors such as Snail, Twist, and ZEB which are mediated by a variety of signaling pathways including TGF-β, Wnt/β-catenin, and Notch. Inhibition of EMT-related molecules and signal pathways in HCC is considered as an important approach to inhibit the invasion and metastasis of HCC. Recent studies have shown that a variety of compound traditional Chinese medicine (TCM) formula or their effective constituents can inhibit the invasion and metastasis of HCC by arresting or reversing EMT in HCC. This article reviews the role and mechanism of EMT and recent studies on TCM drugs and their derived natural compounds in inhibiting the invasion and metastasis of HCC by regulating cell EMT, so as to provide a scientific basis for the TCM prevention and treatment of HCC metastasis and new ideas for HCC treatment.
- Liver Neoplasms /
- Neoplasm Metastasis /
- Epithelial-Mesenchymal Transition /
- Drugs, Chinese Herbal

HTML全文

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

下载: 全尺寸图片幻灯片

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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