Systemic Analysis of the Anticancer Effects of Sijunzi Decoction on Gastric Cancer Based on Network Pharmacology

Objective: Sijunzi decoction (SJZD) has been used for alleviating peptic ulcer or gastric discomfort, and treating spleen disorders since the Song Dynasty, but its pharmacological effect on human gastric cancer (GC) is still unclear. In this research, a network pharmacology-based strategy was applied to explore active ingredients, potential targets, and molecular mechanisms of SJZD against GC. Methods: The active compounds and potential targets of SJZD, as well as GC-associated gene targets, were retrieved from publicly available databases. Bioinformatics approaches were used to assess the network interaction, functional regulation, and signaling pathways between SJZD ingredients and GC targets. The anticancer effects of SJZD against GC were verified in vivo by a mouse subcutaneous model. Results: The results of network analysis showed that quercetin was the most active ingredient in SJZD. Several prominent target genes of SJZD were identified, such as AKT1 and STAT3. Gene ontology analysis revealed that the core anti-GC targets of SJZD included transcription factor activity and kinase activity. Pathway enrichment analysis indicated that GC patients could be benefited from SJZD treatment via modulation of signaling pathways related to endocrine system, cancer, and infectious disease. Furthermore, in vivo experiments showed that high-dose SJZD could inhibit GC xenograft tumor growth, reduce GC cell proliferation, induce GC cell apoptosis, and decrease the expression of p-AKT1 and p-STAT3. Conclusions: Taken together, our results suggest that SJZD can serve as an effective adjuvant therapeutic agent for GC patients.