Huangqi fuling decoction inhibits the invasion and metastasis of gastric cancer via the TNF signaling pathway.

Gastric cancer (GC) is a prevalent digestive tract malignancy, and Huangqi Fuling decoction (HF) has shown potential in enhancing immune function and exhibiting anti-GC activity. However, its mechanisms remain unclear. This study utilized network pharmacology, molecular docking, and in vitro experiments to preliminarily explore the mechanisms by which HF inhibits gastric cancer invasion and metastasis while promoting apoptosis. Public databases identified differentially expressed genes (DEGs), HF targets, and GC-related genes. GO and KEGG analyses revealed signaling pathways. Clinical relevance, immune infiltration, immunotherapy, and molecular docking of hub genes were analyzed. Eight hub genes-PTGS2, MMP9, SELE, CCL2, VCAM1, ICAM1, CXCL2, and CXCL10-associated with the TNF signaling pathway were identified. HF inhibits the invasion and metastasis of GC cells by down-regulating MMP9 and PTGS2 expression, while inducing apoptosis by suppressing BCL-2 expression and promoting BAX expression. Additionally, HF can arrest the cell cycle, blocking AGS cells in the S phase and HGC-27 cells in the G0/G1 phase. This study confirms that HF promotes apoptosis and inhibits metastasis and invasion in GC cells, primarily by modulating the TNF signaling pathway. Additionally, the anti-tumor effects of HF on GC may involve immune regulatory mechanisms, but the mechanism require further experimental verification.