去甲斑蝥素干预胃癌的机制:基于抗肿瘤中成药数据库、网络药理学和转录组学分析。
Mechanism of norcantharidin intervention in gastric cancer: analysis based on antitumor proprietary Chinese medicine database, network pharmacology, and transcriptomics.
发表日期:2024 Sep 17
作者:
Yiyan Zhai, Fanqin Zhang, Jiying Zhou, Chuanqi Qiao, Zhengsen Jin, Jingyuan Zhang, Chao Wu, Rui Shi, Jiaqi Huang, Yifei Gao, Siyu Guo, Haojia Wang, Keyan Chai, Xiaomeng Zhang, Tieshan Wang, Xiaoguang Sheng, Xinkui Liu, Jiarui Wu
来源:
Chinese Medicine
摘要:
抗肿瘤中成药与放疗、化疗相结合,可以有效提高肿瘤治愈率,提高患者的生活质量。胃癌(GC)严重危害公众健康。尽管抗肿瘤中药治疗GC取得了满意的疗效,但其潜在机制仍不清楚。为了整合现有的研究数据,构建抗肿瘤中药数据库,从单体成分出发研究GC的干预机制。我们构建了抗肿瘤中药中药数据库以我国医保目录为基础,采用网络药理学、分子对接方法、细胞实验、转录组学、生物信息学等方法,探讨中药有效成分对GC的干预机制。本研究建立了包含55个中药、171个中国中药的抗肿瘤中药数据库。草药、1955个化学成分、2104个目标和32个疾病信息。网络药理学和分子对接技术鉴定去甲斑蝥素是抗肿瘤中药的有效成分。体外实验表明,去甲斑蝥素能有效抑制GC细胞的增殖、迁移和侵袭;阻断G2/M细胞周期期;并诱导GC细胞凋亡。转录组结果显示,去甲斑蝥素通过影响 PI3K-AKT、NF-κB、JAK-STAT、TNF-α 信号通路和 EMT 相关通路来影响细胞粘附、迁移和炎症反应等生物过程。去甲斑蝥素参与GC干预的核心分子包括SERPINE1、SHOX2、SOX4、PRDM1、TGFR3、TOX、PAX9、IL2RB、LAG3和IL15RA。此外,利用生物信息学方法确定了关键靶点SERPINE1。去甲斑蝥素作为抗肿瘤中药的有效成分,通过影响细胞粘附、迁移、炎症等生物学过程发挥对胃癌的治疗作用。本研究为抗肿瘤中成药的上市后重新评估提供了基础和研究策略。© 2024。作者。
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.To integrate existing research data, construct a database of antitumor pCm, and study the intervention mechanisms in GC by focusing on their monomer components.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.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.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.© 2024. The Author(s).