中药抑制肝细胞癌血管生成的作用机制

李香香; 王振; 杨星; 李素领

doi:10.12449/JCH240729

中药抑制肝细胞癌血管生成的作用机制

DOI: 10.12449/JCH240729

李香香¹,
王振^2a,
杨星¹,
李素领^2b, , ,

1.
河南中医药大学第一临床医学院，郑州 450000
2a.
河南中医药大学第一附属医院科研部，郑州 450000
2b.
河南中医药大学第一附属医院国医堂，郑州 450000

基金项目:

河南省中医管理局科研专项 (20-21ZY1011);

河南省中医管理局科研专项 (2022JDZX048)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：李香香负责课题设计，资料分析，撰写论文；王振、杨星负责修改论文；李素领负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
李素领， hk-lsl@163.com （ORCID： 0000-0002-5211-1330）

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出版历程
- 收稿日期: 2023-11-09
- 录用日期: 2023-12-08
- 出版日期: 2024-07-25

Research advances in the mechanism of action of traditional Chinese medicine in inhibiting angiogenesis in hepatocellular carcinoma

Xiangxiang LI¹,
Zhen WANG^2a,
Xing YANG¹,
Suling LI^{2b
, ,
,}

1.
The First Clinical Medical College of Henan University of Chinese Medicine，Zhengzhou 450000，China
2a.
The First Clinical Medical College of Henan University of Chinese Medicine，Zhengzhou 450000，China
2b.
Department of Scientific Research The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000，China

Research funding:

Henan Provincial Administration of Traditional Chinese Medicine Research Project (20-21ZY1011);

Henan Provincial Administration of Traditional Chinese Medicine Research Project (2022JDZX048)

More Information

Corresponding author: LI Suling， hk-lsl@163.com （ORCID： 0000-0002-5211-1330）

摘要

摘要: 血管生成是肝细胞癌（HCC）发生发展的关键过程，血管新生可为HCC细胞的增殖、侵袭与转移提供必备物质条件。抑制血管生成已成为HCC治疗领域的研究热点。中药以多靶点、多途径、增效减毒、改善肿瘤预后以及延长生存期的特点成为抗HCC治疗的潜力药物。经现代研究证实，中药可通过抑制促血管生长因子表达、上调抗血管生成因子水平、抑制内皮细胞增殖、降低HCC组织微血管密度和调控相关信号通路等作用机制抑制肿瘤血管生成，在HCC的治疗方面具有独特优势。本文通过梳理并总结近年来国内外相关文献，分析中药抑制HCC血管生成的作用机制，以期为临床HCC治疗策略的优化提供一定的理论依据和参考。
- 瘤，肝细胞 /
- 血管生成诱导剂 /
- 血管生成抑制剂 /
- 中草药
Abstract: Angiogenesis is a key process in the development and progression of hepatocellular carcinoma （HCC） and can provide essential material conditions for the proliferation， invasion， and metastasis of HCC cells. Inhibition of angiogenesis has become a research hotspot in the field of HCC therapy. Traditional Chinese medicine has become a potential drug for HCC therapy due to its characteristics of multiple targets and pathways， enhancing efficacy and reducing toxicity， improving tumor prognosis， and prolonging survival time. Modern studies have confirmed that traditional Chinese medicine can inhibit tumor angiogenesis by inhibiting the expression of angiogenic factors， upregulating the levels of anti-angiogenic factors， inhibiting endothelial cell proliferation， reducing the microvascular density of HCC tissue， and regulating related signaling pathways， and therefore， traditional Chinese medicine has unique advantages in the treatment of HCC. By summarizing related articles in China and globally in recent years， this article analyzes the mechanism of action of traditional Chinese medicine on inhibiting HCC angiogenesis， in order to provide certain theoretical basis and reference for the optimization of HCC treatment strategies in clinical practice.
- Carcinoma， Hepatocellular /
- Angiogenesis Inducing Agents /
- Angiogenesis Inhibitors /
- Drugs， Chinese Herbal

HTML全文

图 1 JAK2/STAT3信号通路

Figure 1. JAK2/STAT3 signaling pathway

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图 2 PI3K/Akt信号通路

Figure 2. PI3K/Akt signaling pathway

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图 3 NF-κB信号通路

Figure 3. NF-κB signaling pathway

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表 1 中药调节促血管生成因子和抗血管生成因子的作用

Table 1. Role of traditional Chinese medicine in regulating pro-angiogenic factors and inhibiting angiogenesis inhibition

中药复方或活性成分	实验模型	作用机制	文献
表没食子儿茶素没食子酸酯	H₂₂肝癌荷瘤小鼠	抑制VEGF表达	［20］
美洲大蠊多肽PAE₂	HepG2/ADM移植瘤裸鼠	降低VEGF表达	［21］
白花丹醌	人肝癌HepG2细胞	下调HIF-1α蛋白，抑制MMP-9表达	［24］
香菇多糖	肝癌细胞BEL-7402/S	VEGF和HIF-1α表达下调	［25］
SDSF	人肝癌HepG2细胞	降低MMP-2、MMP-9活性	［27］
柔肝化纤解毒颗粒	肝癌患者	降低HIF-1α、VEGF、MMP-2、MMP-9表达	［28］
丹参酮ⅡA	人肝癌SMMC-7721细胞株	抑制Ang-2及其受体Tie-2表达	［31］
柴胡皂苷d	人肝癌BEL-7402细胞	抑制VEGF、Ang-2蛋白表达	［32］
参苓白术散	H₂₂肝癌移植瘤小鼠	沉默Ang-2表达	［33］
癌毒清颗粒	肝癌模型小鼠	下调VEGF、HIF-α、bFGF表达	［34］
当归贝母苦参丸加味方	H₂₂荷瘤小鼠	下调bFGF表达	［37］
毒痰瘀脾虚方	肝癌患者	下调血清中b-FGF、VEGF水平	［38］
十全大补汤	小鼠肝癌细胞CT-26	上调AS、ES表达，下调VEGF水平	［41］
二鳖散	Walker-256肝癌大鼠	调控VEGF/ES的失衡	［42］

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表 2 中药抑制内皮细胞增殖及降低肝癌组织MVD的作用

Table 2. Role of traditional Chinese medicine in reducing microvascular density

中药复方或活性成分	实验模型	作用机制	文献
三七提取液	人肝癌HepG2细胞株、HUVEC	抑制HepG2肝癌细胞和HUVEC增殖	［44］
吴茱萸碱	人肝癌HepG2细胞、HUVEC	抑制HUVEC和HepG2细胞增殖，诱导HUVEC凋亡	［45］
白花丹素	人内皮细胞系EA.hy926、人肝癌细胞系SMMC-7721和Hep3B	抑制EA.hy926细胞的增殖、迁移和侵袭	［46］
丹参酮ⅡA	Hepa1-6肝癌小鼠	降低MVD	［49］
参麦注射液	肝癌患者	降低MVD，抑制VEGF表达	［50］
GQN	H₂₂荷瘤小鼠	抑制MVD和VEGF的表达	［51］

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表 3 中药调节相关通路的作用

Table 3. Role of TCM in regulating related pathways

中药复方或活性成分	实验模型	作用机制	文献
荷包牡丹碱	人肝癌MHCC97-H细胞	抑制JAK2/STAT3信号通路的活化，下调VEGF、MMP-2、MMP-9基因表达	［55］
复方苦参注射液	肝癌HepG2细胞	抑制JAK2/STAT3信号通路，降低MMP-2、MMP-9表达	［56］
复方苦参注射液	LPC-H12肝癌细胞异种移植瘤斑马鱼	阻断PI3K/Akt通路的活化	［59］
山慈菇多糖	肝癌腹水荷瘤小鼠	抑制PI3K/Akt通路激活，抑制肿瘤血管生成	［60］
地锦草	H₂₂肝癌小鼠	调控NF-κB信号通路，降低VEGF mRNA和蛋白表达	［63］
紫葛花青素	人肝癌Hep3B细胞移植瘤小鼠	抑制NF-κB信号通路表达，降低MMP-2、MMP-9表达水平	［64］

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