Network pharmacology analysis and clinical efficacy study of Fuzi Lizhong Decoction combined with XELOX plus sintilimab in the treatment of advanced gastric cancer

This study aimed to evaluate the clinical efficacy of Fuzi Lizhong Decoction (FZLZD) as an adjunct therapy for advanced gastric cancer (GC) when combined with the capecitabine plus oxaliplatin (XELOX) plus sintilimab regimen and to elucidate its potential therapeutic mechanisms through network pharmacology. Network pharmacology was employed to identify active ingredients of FZLZD and predict key targets and signaling pathways involved in GC treatment. GeneMANIA-based Functional Association analysis, core microRNA screening, and immunohistochemical analysis of core proteins were performed. Molecular docking was used to verify the direct regulatory effects of these traditional Chinese medicine monomers on the targets. FZLZD was found to have 732 targets associated with GC, involving processes such as protein phosphorylation, signal transduction, and gene transcription regulation. These targets were enriched in tumor- and metabolism-related pathways. The core proteins included protein tyrosine phosphatase non-receptor type 1, estrogen receptor 2, cytochrome P450 family 19 subfamily A member 1, and interleukin 6, while the core drug monomers included glypallichalcone, α-amyrin, deoxyharringtonine, and neokadsuranic acid B. Molecular docking results showed strong binding between the core targets and monomers. Clinical comparative studies have shown that compared with the XELOX plus sintilimab regimen alone, the combination of FZLZD and this regimen can significantly reduce traditional Chinese medicine symptom scores, lower tumor marker levels, and interleukin 6 levels in the treatment of advanced GC, and meaningfully improve health-related quality of life metrics. This study provides preliminary evidence that FZLZD, when combined with the XELOX plus sintilimab regimen, enhances the efficacy of the treatment for advanced GC. The results suggest that FZLZD may modulate key targets and signaling pathways, offering insights for further research and clinical application.