利用数据挖掘和系统药理学方法阐明中药治疗原发性肝癌的疗效和机制

Zhen ZHANG; Jun-wei LI; Pu-hua ZENG; Wen-hui GAO; Xue-fei TIAN

doi:10.1007/s11655-021-3449-8

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利用数据挖掘和系统药理学方法阐明中药治疗原发性肝癌的疗效和机制

Original Article | Updated：2022-06-27

- 利用数据挖掘和系统药理学方法阐明中药治疗原发性肝癌的疗效和机制
- Data Mining and Systems Pharmacology to Elucidate Effectiveness and Mechanisms of Chinese Medicine in Treating Primary Liver Cancer
- Chinese Journal of Integrative Medicine 2022年28卷第7期页码：636-643
- Affiliations：
  
  1.Department of Internal Medicine, College of Integrated Chinese and Western Medicine of Hunan University of Chinese Medicine, Changsha (410208), China
  2.Hunan Key Laboratory of TCM Prescription and Syndromes Translational Medicine,Hunan University of Chinese Medicine, Changsha (410208),China
  3.Department of Pharmacy, Shenzhen People's Hospital(the Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen (518020), Guangdong Province, China
  4.Department of Oncology, Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha (410006),China
- Author bio：
  
  Prof. TIAN Xue-fei, E-mail: 003640@hnucm.edu.cn
- Funds：
  
  the National Natural Science Foundation of China(82074450);Natural Science Foundation of Hunan Province(2020JJ4066);Postgraduate Innovation Project of Hunan University of Chinese Medicine in 2020(2020CX14);"YIFANG" Postgraduate Innovation Project of Hunan University of Chinese Medicine(2020YF04)
- DOI：10.1007/s11655-021-3449-8
  中图分类号：
- 纸质出版日期：2022-07-01，
  
  网络出版日期：2021-08-25，
  
  录用日期：2021-04-02
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Zhen ZHANG, Jun-wei LI, Pu-hua ZENG, 等. 利用数据挖掘和系统药理学方法阐明中药治疗原发性肝癌的疗效和机制[J]. Chinese Journal of Integrative Medicine, 2022,28(7):636-643.

Zhen ZHANG, Jun-wei LI, Pu-hua ZENG, et al. Data Mining and Systems Pharmacology to Elucidate Effectiveness and Mechanisms of Chinese Medicine in Treating Primary Liver Cancer[J]. Chinese Journal of Integrative Medicine, 2022,28(7):636-643.
Zhen ZHANG, Jun-wei LI, Pu-hua ZENG, 等. 利用数据挖掘和系统药理学方法阐明中药治疗原发性肝癌的疗效和机制[J]. Chinese Journal of Integrative Medicine, 2022,28(7):636-643. DOI： 10.1007/s11655-021-3449-8.

Zhen ZHANG, Jun-wei LI, Pu-hua ZENG, et al. Data Mining and Systems Pharmacology to Elucidate Effectiveness and Mechanisms of Chinese Medicine in Treating Primary Liver Cancer[J]. Chinese Journal of Integrative Medicine, 2022,28(7):636-643. DOI： 10.1007/s11655-021-3449-8.

摘要

目的:

确定可能对原发性肝癌患者有益的特定中药

并探讨这些药物的作用机制.

方法:

这是一项回顾性、单中心研究

利用肝癌患者的处方信息与传统中医传承支持系统相结合

确定特定核心药

并采用系统药理学方法探索这些药物的作用机制.

结果:

服用中药6 个月以上与改善肝癌患者生存结果显著相关. 共确认特定核心药物的 77 个推定靶标和 116 种生物活性成分

并将其纳入分析. 共发现1036 个Gene Ontology术语在肝癌中富集

从 Kyoto Encyclopedia of Genes 和Genomes 共鉴定出 75 条通路

包括流体剪切应力、白细胞介素17 信号传导、晚期聚糖终产物及其受体之间的信号传导、细胞衰老、肿瘤坏死因子信号传导、p53 信号传导、细胞周期信号、类固醇激素生物合成、T-helper 17 细胞分化和细胞色素对异生素的代谢. 对接研究表明

特定核心药物的成分通过调节 c-Jun 和白细胞介素 6 在肝癌中发挥治疗作用.

结论:

中药治疗6个月以上可提高肝癌患者的生存率. 真正对肝癌患者有益的特定核心药物可能通过调节肿瘤微环境和肿瘤本身发挥作用.

Abstract

Objective:

To identify specific Chinese medicines (CM) that may benefit patients with primary liver cancer (PLC)

and to explore the mechanism of action of these medicines.

Methods:

In this retrospective

singlecenter study

prescription information from PLC patients was used in combination with Traditional Chinese Medicine Inheritance Supports System to identify the specific core drugs. A system pharmacology approach was employed to explore the mechanism of action of these medicines.

Results:

Taking CM more than 6 months was significantly associated with improved survival outcomes. In total

77 putative targets and 116 bioactive ingredients of the core drugs were identified and included in the analysis (

0.05). A total of 1

036 gene ontology terms were found to be enriched in PLC. A total of 75 pathways identified from Kyoto Encyclopedia of Genes and Genomes were also enriched in this disease

including fluid shear stress

interleukin-17 signaling

signaling between advanced glycan end products and their receptors

cellular senescence

tumor necrosis factor signaling

p53 signaling

cell cycle signaling

steroid hormone biosynthesis

T-helper 17 cell differentiation

and metabolism of xenobiotics by cytochrome. Docking studies suggested that the ingredients in the core drugs exert therapeutic effects in PLC by modulating c-Jun and interleukin-6.

Conclusions:

Receiving CM for 6 months or more improves survival for the patients with PLC. The core drugs that really benefit for PLC patients likely regulates the tumor microenvironment and tumor itself.

关键词

Keywords

Chinese medicineprimary liver cancersystem pharmacologybioinformaticstumor microenvironment

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