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

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.