中药调控肿瘤相关巨噬细胞对肝细胞癌的治疗作用与机制

唐怡; 王国泰; 蒋雨涵; 吴晨旸

doi:10.12449/JCH250630

中药调控肿瘤相关巨噬细胞对肝细胞癌的治疗作用与机制

DOI: 10.12449/JCH250630

唐怡¹,
王国泰^2, , ,,
蒋雨涵¹,
吴晨旸¹

1.
陕西中医药大学第一临床医学院，陕西咸阳 712046
2.
陕西中医药大学附属医院肝胆外科，陕西咸阳 712099

基金项目:

陕西省中医药管理局中医药科研项目 (SZY-KJCYC-2025-JC-004);

秦创原中医药产业创新聚集区项目 (L2024-QCY-ZYYJJQ-Y09);

咸阳市中青年科技领军人才项目 (L2022CXNLRC018);

咸阳市科学技术局重点研发项目 (2021ZDYF-SF-0037)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：唐怡参与研究设计，资料分析，撰写论文；王国泰负责分析相关材料，修改论文；蒋雨涵、吴晨旸检索并收集相关文献。

详细信息

通信作者:
王国泰， wangtai_52@126.com （ORCID： 0009-0009-5405-9351）

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出版历程
- 收稿日期: 2024-09-27
- 录用日期: 2024-10-21
- 出版日期: 2025-06-25

Therapeutic effect of traditional Chinese medicine in liver cancer by regulating tumor-associated macrophages and its mechanism

1.
The First Clinical Medical College，Shaanxi University of Chinese Medicine，Xianyang，Shaanxi 712046，China
2.
Department of Hepatobiliary Surgery，The Affiliated Hospital of Shaanxi University of Chinese Medicine，Xianyang，Shaanxi 712099，China

Research funding:

Traditional Chinese Medicine Scientific Research Project of Shaanxi Provincial Administration of Traditional Chinese Medicine (SZY-KJCYC-2025-JC-004);

Qin Chuangyuan Traditional Chinese Medicine Industry Innovation Aggregation Zone Project (L2024-QCY-ZYYJJQ-Y09);

Young and Middle-aged Scientific and Technological Leading Talents Project of Xianyang City (L2022CXNLRC018);

Key R&D Project of Xianyang Science and Technology Bureau (2021ZDYF-SF-0037)

More Information

Corresponding author: WANG Guotai， wangtai_52@126.com （ORCID： 0009-0009-5405-9351）

摘要

摘要: 肝细胞癌（HCC）作为全球性高发病率、高病死率的疾病，其发生发展与肿瘤微环境和肿瘤相关巨噬细胞（TAM）的相互作用密切相关。TAM在HCC免疫抑制、免疫逃逸、细胞增殖、侵袭和转移以及药物耐受性方面发挥着重要作用。中药凭借其独特的治疗理念和方法，在调控TAM、改善HCC预后方面展现出巨大潜力。本文综述了中药调控TAM在HCC治疗中的作用及其分子机制，探讨了TAM在HCC进展中的关键作用，并基于中医理论，系统分析了中药成分对TAM募集、极化、活性及相关因子表达的影响。当前研究发现，中药可通过调节TAM的极化状态，促进M1型抗肿瘤巨噬细胞的形成，抑制M2型肿瘤巨噬细胞的活性，从而在抑制HCC细胞增殖、促进凋亡、抗血管生成和增强免疫应答等方面发挥作用。此外，本文还总结了中药单体、复方及新型制剂在HCC治疗中的分子靶点和作用机制，如通过抑制TAM分泌细胞因子、调节信号通路、影响代谢途径等，为中药在HCC治疗中的应用提供了科学依据，同时为HCC的免疫治疗提供了新思路。
- 肝肿瘤 /
- 肿瘤相关巨噬细胞 /
- 中药
Abstract: Liver cancer has high prevalence and mortality rates around the world， and its development and progression are closely associated with the interaction between the tumor microenvironment and tumor-associated macrophages （TAMs）. TAMs play a significant role in immune suppression， immune escape， cell proliferation， invasion， metastasis， and drug resistance in liver cancer. Traditional Chinese medicine （TCM）， with its unique therapeutic concepts and methods， has shown great potential in regulating TAMs and improving the prognosis of liver cancer. This article reviews the role and molecular mechanisms of TCM in regulating TAMs for the treatment of liver cancer， discusses the key role of TAMs in the progression of liver cancer， and analyzes the impact of Chinese medicinal components on the recruitment， polarization， and activity of TAMs and the expression of related factors based on TCM theory. Studies have shown that TCM can regulate the polarization state of TAMs， promote the formation of M1-type antitumor macrophages， and inhibit the activity of M2-type tumor macrophages， thereby playing a role in inhibiting the proliferation of liver cancer cells， promoting apoptosis， inhibiting angiogenesis， and enhancing immune response. In addition， this article also summarizes the molecular targets and mechanisms of action of TCM monomers， compound prescriptions， and novel preparations in the treatment of liver cancer， such as inhibiting the secretion of cytokines by TAMs， regulating signaling pathways， and affecting metabolic pathways， in order to provide a scientific basis for the application of TCM in liver cancer treatment and offer new ideas for immunotherapy for liver cancer.
- Liver Neoplasms /
- Tumor-Associated Macrophages /
- Traditional Chinese Drugs

HTML全文

注： TNF-α，肿瘤坏死因子-α；IL，白细胞介素；CXCL/CCL，趋化因子配体；TGF-β，转化生长因子-β；VEGF，血管内皮生长因子。

图 1 TAM的来源、分类及功能

Figure 1. Origin， classification， and functions of tumor-associated macrophages

下载: 全尺寸图片幻灯片

表 1 中药单体及其活性成分调控TAM的作用机制

Table 1. Mechanisms of action of traditional Chinese medicine monomers and their active components in regulating TAM

分类	中药活性成分	来源	实验类型	实验模型（细胞/动物）	作用机制（TAM极化方向+信号通路）	参考文献
生物碱类	澳洲茄边碱	龙葵	体内	BALB/c裸鼠	M1↓，M2↑，抑制LIF/miR-192-5p/CYR61/ Akt信号轴，诱导HCC细胞的凋亡和自噬	［30］
	岩黄连总生物碱	岩黄连	体内	昆明小鼠	M1↑，M2↓，抑制PI3K/Akt信号通路和 HCC细胞的生长	［31］
	青藤碱	青风藤	体内+体外	昆明小鼠+RAW264.7细胞+ H22细胞	M1↑，M2↓，下调α7nAChR的表达，抑制 HCC细胞的生长	［32］
蒽醌类	大黄素	大黄、芦荟等	体外+体内	HepG2细胞+Huh7细胞+ THP-1细胞+BALB/c裸鼠	M1↑，M2↓，抑制miR-26a/TGF-β1/Akt 信号通路和HCC细胞的增殖和侵袭	［34］
苯酞类	藁本内酯	川芎、当归	体外	HepG2+THP-1+HL-7702 细胞	M2↓，抑制IL-6受体/STAT3信号通路和 HCC进展	［35］
萜类	斑蝥素	斑蝥	体内	BALB/c裸鼠	M1↑，M2↓，通过抑制β-catenin和STAT3 信号通路来抑制肿瘤细胞生存和侵袭	［36］
黄酮类	槲皮素	黄芩、槐花等	体外+体内	H22细胞+HepG2细胞+ BALB/c裸鼠	M1↑，M2↓，通过调节巨噬细胞极化，协同NF-κB通路调节自噬，抑制HCC发展	［39］
黄酮类	黄芩苷	黄芩	体内+体外	BALB/c裸鼠+MHCC97L细胞	M1↑，M2↓，通过自噬诱导RelB/p52 信号通路的激活，抑制HCC的发展	［40］
甾体类	蟾毒灵	蟾蜍	体内+体外	C57BL/6小鼠+BALB/c裸鼠+ Hepa1-6细胞	M1↑，M2↓，激活NF-κB信号通路和免疫反应，抑制HCC的发生	［41］
甾体类	cynsaccatol L	甘遂	体外	HepG2细胞+RAW264.7细胞	M2↓，抑制Akt/ERK信号通路，诱导HCC 细胞的凋亡	［42］
皂苷类	黄芪甲苷Ⅳ	黄芪	体内+体外	BALB/c裸鼠+Huh-7细胞+ THP-1细胞	M1↑，M2↓，抑制TLR4/NF-κB/STAT3 信号通路和HCC细胞的生长和侵袭	［43］
多糖类	灵芝多糖	灵芝	体内+体外	C57BL/6小鼠+RAW264.7 细胞	M1↑，M2↓，激活MAPK/NF-κB信号通路，抑制HCC的发展	［44］
多糖类	灵芝孢子粉多糖	灵芝孢子	体外	BALB/c裸鼠	M1↑，M2↓，抑制PI3K/Akt信号通路，诱导HCC细胞的凋亡	［45］
酚类	单宁	毛诃子	体内+体外	C57BL/6小鼠+BMDM细胞	M1↑，M2↓，增强CD8⁺ T细胞的细胞毒性功能	［46］
注：↓表示减少；↑表示增加；CYR61，富含半胱氨酸蛋白61。

下载: 导出CSV

表 2 中药复方及配伍药调控TAM的作用机制

Table 2. Mechanisms of action of traditional Chinese medicine formulas and compatible herb pairs in regulating TAM

复方	组成	实验类型	实验模型（细胞/动物）	作用机制（TAM极化方向+信号通路）	参考文献
参莲汤	党参、陈皮、半枝莲	体内+体外	C57BL/6小鼠+ Hepa1-6细胞	M1↑，M2↓，抑制AMPK/p38信号通路，减少免疫抑制微环境的形成	［47］
西黄丸	牛黄、麝香、醋制乳香和醋制没药	体外+体内	HepG2细胞+ 昆明小鼠	M1↓，M2↑，促进癌细胞的凋亡；调节PD-1/PD- L1信号通路，抑制免疫逃逸	［48］
益脾养肝方	白术、党参、熟地黄、鳖甲、枸杞子、半枝莲、郁金、姜黄、白花蛇舌草	体内	Wistar雄性大鼠	M1↓，通过调节免疫反应和抗炎作用，显示出对 HCC前病变的潜在治疗作用	［49］
黄芩汤	黄芩、白芍、甘草、大枣	体内	BALB/c裸鼠	M1↑，促进肿瘤细胞凋亡，调节TME中的炎症和自噬过程，增强巨噬细胞浸润以及激活ERK1/2 信号通路，增强索拉非尼的抗HCC作用	［50］

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