Determining the Mechanism of Banxia Xiexin Decoction for Gastric Cancer Treatment through Network Analysis and Experimental Validation.

Abstract

Gastric cancer (GC) is a widespread malignancy. Banxia Xiexin decoction (BXD) has been used for GC treatment, but the specific mechanisms underlying its therapeutic effects remain controversial. This study used a comprehensive approach to network pharmacology combined with experimental validation to elucidate the mechanism of BXD's anti-GC effects. Initially, we used the UHPLC-LTQ-Orbitrap-MS/MS technology to identify the main chemical constituents of BXD, as well as potential targets associated with these constituents. Then, we employed the Genecard and Online Mendelian Inheritance in Man (OMIM) to determine the targets specifically related to GC. We employed a combination of Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes pathway, and protein-protein interaction analysis to predict the crucial targets of BXD and uncover the pathways involved in its therapeutic effects against GC. The results were subsequently verified through cell experiments. The analysis revealed 174 common targets shared by BXD and GC. GO enrichment analysis highlighted biological processes, such as autophagy, protein kinase activity, and apoptosis. Moreover, the enrichment analysis revealed several significant pathways that serve as the primary mechanisms by which BXD exerts its effects. Notably, these pathways include PI3K-Akt, HIF-1, and Pathways in cancer. Subsequent in vitro experiments demonstrated that BXD effectively hindered GC cell proliferation, stimulated autophagy, and facilitated apoptosis by PI3K-Akt-mTOR signaling pathway regulation. These findings reveal the effectiveness of BXD against GC through diverse components, targets, and pathways, indicating that BXD holds potential therapeutic value in GC treatment. This study uncovers the intricate biological mechanisms that underlie BXD's efficacy in treating GC through the integration of network pharmacology analysis and rigorous in vitro experiments.