Abstract
BACKGROUND: Weiqi Decoction (WQD) is an empirical prescription traditionally used in China for the treatment of precancerous gastric cancer (GC) lesions. This study aimed to elucidate the potential pharmacological mechanisms of WQD in GC therapy. METHODS: Active ingredients, corresponding targets, and GC-related genes were identified using public databases. A protein-protein interaction (PPI) network was constructed via the STRING database, and functional enrichment analyses were conducted using the DAVID platform. Gene expression and survival analyses were performed using the GEPIA database. Molecular docking was conducted with AutoDock Vina and visualized using PyMOL. The effects of WQD on GC cell viability, proliferation, migration, and invasion were evaluated through CCK-8, colony formation, and Transwell assays. RESULTS: WQD contained 43 active ingredients targeting 751 potential genes, including 458 GC-related targets. Quercetin, luteolin, and kaempferol were identified as key active compounds. PPI network analysis revealed nine core targets, including TP53 and SRC, which may mediate the anti-GC effects of WQD. GO enrichment analysis indicated involvement in 726 biological processes, 91 cellular components, and 177 molecular functions, while KEGG pathway analysis suggested modulation of the AGE-RAGE, PI3K-Akt, and HIF-1 signaling pathways. GEPIA database analysis confirmed that EP300, HSP90AA1, HSP90AB1, SRC, and TP53 were highly expressed in GC. Molecular docking demonstrated strong binding affinities between the key active compounds and core targets. In vitro experiments further validated that WQD extract inhibited GC cell viability, proliferation, migration, and invasion. CONCLUSION: WQD exhibits therapeutic potential against GC by regulating multiple targets and signaling pathways. These findings provide mechanistic insights into the pharmacological actions of WQD in GC treatment.