去甲斑蝥素干预胃癌的机制：基于抗肿瘤中药数据库、网络药理学和转录组学的分析

Mechanism of norcantharidin intervention in gastric cancer: analysis based on antitumor proprietary Chinese medicine database, network pharmacology, and transcriptomics.

作者信息

Zhai Yiyan, Zhang Fanqin, Zhou Jiying, Qiao Chuanqi, Jin Zhengsen, Zhang Jingyuan, Wu Chao, Shi Rui, Huang Jiaqi, Gao Yifei, Guo Siyu, Wang Haojia, Chai Keyan, Zhang Xiaomeng, Wang Tieshan, Sheng Xiaoguang, Liu Xinkui, Wu Jiarui

机构信息

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China.

Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.

出版信息

Chin Med. 2024 Sep 17;19(1):129. doi: 10.1186/s13020-024-01000-1.

DOI:10.1186/s13020-024-01000-1

PMID:39289763

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11406961/

Abstract

BACKGROUND

Combining antitumor proprietary Chinese medicine (pCm) with radiotherapy and chemotherapy can effectively improve tumor cure rates and enhance patients' quality of life. Gastric cancer (GC) severely endangers public health. Despite satisfactory therapeutic effects achieved by using antitumor pCm to treat GC, its underlying mechanism remains unclear.

OBJECTIVE

To integrate existing research data, construct a database of antitumor pCm, and study the intervention mechanisms in GC by focusing on their monomer components.

METHODS

We constructed an antitumor pCm database based on China's medical insurance catalog, and employed network pharmacology, molecular docking methods, cell experiments, transcriptomics, and bioinformatics to investigate the intervention mechanisms of effective pCm components for GC.

RESULTS

The study built an antitumor pCm database including 55 pCms, 171 Chinese herbal medicines, 1955 chemical components, 2104 targets, and 32 disease information. Network pharmacology and molecular docking technology identified norcantharidin as an effective component of antitumor pCm. In vitro experiments showed that norcantharidin effectively inhibited GC cell proliferation, migration, and invasion; blocked the G2/M cell cycle phase; and induced GC cell apoptosis. Transcriptomic results revealed that norcantharidin affected biological processes, such as cell adhesion, migration, and inflammatory responses by influencing PI3K-AKT, NF-κB, JAK-STAT, TNF-α signaling pathways, and EMT-related pathways. Core molecules of norcantharidin involved in GC intervention include SERPINE1, SHOX2, SOX4, PRDM1, TGFR3, TOX, PAX9, IL2RB, LAG3, and IL15RA. Additionally, the key target SERPINE1 was identified using bioinformatics methods.

CONCLUSION

Norcantharidin, as an effective component of anti-tumor pCm, exerts its therapeutic effects on GC by influencing biological processes such as cell adhesion, migration, and inflammation. This study provides a foundation and research strategy for the post-marketing re-evaluation of antitumor pCms.

摘要

背景

抗肿瘤中成药（pCm）与放疗、化疗联合应用可有效提高肿瘤治愈率，提升患者生活质量。胃癌（GC）严重危害公众健康。尽管使用抗肿瘤pCm治疗GC取得了满意的疗效，但其潜在机制仍不清楚。

目的

整合现有研究数据，构建抗肿瘤pCm数据库，并聚焦其单体成分研究在GC中的干预机制。

方法

基于中国医保目录构建抗肿瘤pCm数据库，运用网络药理学、分子对接方法、细胞实验、转录组学和生物信息学研究有效pCm成分对GC的干预机制。

结果

本研究构建了一个包含55种pCm、171味中药材、1955种化学成分、2104个靶点和32条疾病信息的抗肿瘤pCm数据库。网络药理学和分子对接技术确定去甲斑蝥素为抗肿瘤pCm的有效成分。体外实验表明，去甲斑蝥素能有效抑制GC细胞增殖、迁移和侵袭；阻断G2/M细胞周期阶段；诱导GC细胞凋亡。转录组学结果显示，去甲斑蝥素通过影响PI3K-AKT、NF-κB、JAK-STAT、TNF-α信号通路和EMT相关通路，影响细胞黏附、迁移和炎症反应等生物学过程。去甲斑蝥素干预GC的核心分子包括SERPINE1、SHOX2、SOX4、PRDM1、TGFR3、TOX、PAX9、IL2RB、LAG3和IL15RA。此外，利用生物信息学方法鉴定了关键靶点SERPINE1。