《肿瘤良方大全》中肝癌用药规律挖掘及其核心药对机制分析

doi:10.5246/jcps.2024.07.048

摘要/Abstract

摘要：

本研究挖掘了《肿瘤良方大全》中肝癌治疗复方的组方规律, 并探讨了核心药对的作用机制。首先我们摘录了书中肝癌治疗复方, 利用Excel 2017统计用药频次、性味、归经等; 利用IBM SPSS Modeler18.0进行中药关联规则分析, 并使用Cytoscape 3.7.2进行可视化展示; 通过TCMSP、TCMID、Genecards、DAVID等数据库对核心药对的作用机制进行网络药理学分析。结果共纳入复方131个, 涉及中药303味, 核心中药以活血化瘀类、清热类和补虚类为主, 药味多见苦、辛, 并多为寒性, 且多入肝经、脾经。关联分析显示, 当归-鳖甲的支持度最高。网络药理学预测到当归-鳖甲抗肝癌核心靶点20个, 主要包括IL-6、MAPK3、SRC等。基因生存分析显示肝癌患者MAPK3、SRC高表达且预后生存率较差; KEGG分析显示当归-鳖甲抗肝癌的主要通路包括癌症通路、TNF信号通路、催乳素信号通路等。研究发现中药治疗肝癌以活血化瘀药、清热药和补虚药为主; 当归-鳖甲是中药治疗肝癌的核心药对, 其机制可能是通过影响MAPK3、SRC等关键基因, 调控癌症通路、TNF信号通路、催乳素信号通路等发挥作用。

关键词: 肿瘤良方大全, 肝癌, 当归, 鳖甲, 数据挖掘, 网络药理学

Abstract:

This study delved into the formulaic patterns of liver cancer treatment outlined in "The Complete Book of Good Tumor Prescriptions" and explored the action mechanisms of core traditional Chinese medicine (TCM) combinations. Initially, liver cancer treatment formulas were extracted from the aforementioned book, and Excel 2017 was employed for calculating the frequency, properties, and meridians associated with the TCMs. IBM SPSS Modeler 18.0 was utilized for the analysis of TCM association rules, and Cytoscape 3.7.2 was employed for the visualization of these rules. Subsequently, network pharmacology was utilized to analyze the action mechanisms of core TCM combinations, leveraging TCMSP, TCMID, Genecards, DAVID, and other databases. The results revealed the inclusion of 131 prescriptions encompassing 303 TCMs. The core TCMs predominantly comprised those invigorating blood circulation and removing blood stasis, clearing heat, and tonifying deficiencies. The flavor of the TCMs was chiefly bitter or pungent, with a prevailing cold property entering the liver and spleen meridians. Association analysis indicated that the support of Angelicae sinensis radix-Trionycis carapax was the highest. Network pharmacology predictions indicated that Angelicae sinensis radix-Trionycis carapax possessed 20 target genes associated with anti-liver cancer properties, including IL-6, MAPK3, and SRC. Gene survival analysis demonstrated high expression of MAPK3 and SRC in liver cancer patients, correlating with a poor prognosis. KEGG analysis identified major anti-liver cancer pathways for Angelicae sinensis radix-Trionycis carapax, encompassing the cancer pathway, TNF signaling pathway, and prolactin signaling pathway. In summary, this study elucidated that TCMs for liver cancer treatment primarily consisted of invigorating blood circulation and removing blood stasis, antipyretic, and tonifying medicines. The core TCM pair, Angelicae sinensis radix-Trionycis carapax, appeared pivotal in this context. The underlying mechanism might involve the modulation of key genes, such as MAPK3 and SRC, and the regulation of pathways, including the cancer pathway, TNF signaling pathway, and prolactin signaling pathway.

Key words: The Complete Book of Good Tumor Prescriptions, Liver cancer, Angelicae sinensis radix, Trionycis carapax, Data mining, Network pharmacology

Supporting:

张啸, 钟叶, 胡永生, 王博龙. 《肿瘤良方大全》中肝癌用药规律挖掘及其核心药对机制分析[J]. 中国药学(英文版), 2024, 33(7): 647-658.

Xiao Zhang, Ye Zhong, Yongsheng Hu, Bolong Wang. Optimizing medication strategies for liver cancer: unraveling the mechanisms of key drug combinations in the comprehensive guide to effective tumor prescriptions[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(7): 647-658.

图/表 11

Figure 1. Screening process of core TCMs.

Figure 2. Network diagram of core TCM's property-meridian-efficacy.

Table 1. The usage frequency and efficacy of core TCMs.

Table 2. Association rules of TCMs.

Figure 3. Co-occurrence diagram of association rules.

Figure 4. Load diagram of factor analysis.

Table 3. Distribution of common factors.

Figure 5. Screening diagram of key targets.

Figure 6. Survival curve of liver cancer patients and gene expression (*P < 0.05).

Figure 7. Gene expression levels between liver cancer tissues and normal tissues (*P < 0.05).

Figure 8. Bubble chart of KEGG pathway analysis.

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