Published online Jan 15, 2024. doi: 10.4251/wjgo.v16.i1.30
Peer-review started: July 29, 2023
First decision: September 25, 2023
Revised: October 7, 2023
Accepted: November 2, 2023
Article in press: November 2, 2023
Published online: January 15, 2024
Processing time: 165 Days and 22.5 Hours
Pachymic acid (PA) is derived from Poria cocos. PA has a variety of pharmacological and inhibitory effects on various tumors. However, the mechanism of action of PA in gastric cancer (GC) remains unclear.
To investigate the mechanism of PA in treating GC via the combination of network pharmacology and experimental verification.
The GeneCards and OMIM databases were used to derive the GC targets, while the Pharm Mapper database provided the PA targets. Utilizing the STRING database, a protein-protein interaction network was constructed and core targets were screened. The analyses of Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis were conducted, and molecular docking and clinical correlation analyses were performed on the core targets. Ultimately, the network pharmacology findings were validated through in vitro cell assays, encompassing assessments of cell viability, apoptosis, cell cycle, cloning, and western blot analysis.
According to network pharmacology analysis, the core targets were screened, and the PI3K/AKT signaling pathway is likely to be the mechanism by which PA effectively treats GC, according to KEGG enrichment analysis. The experimental findings showed that PA could control PI3K/AKT signaling to prevent GC cell proliferation, induce apoptosis, and pause the cell cycle.
Network pharmacology demonstrated that PA could treat GC by controlling a variety of signaling pathways and acting on a variety of targets. This has also been supported by in vitro cell studies, which serve as benchmarks for further research.
Core Tip: Pachymic acid (PA) is an important bioactive component of Poria cocos. Network pharmacology analysis showed that the core targets of PA in treating gastric cancer (GC) were proto-oncogene tyrosine-protein kinase Src, mitogen-activated protein kinase 1, phosphatidylinositol 3-kinase regulatory subunit alpha, heat shock protein 90-alpha, and tyrosine-protein phosphatase non-receptor type 11. Molecular docking results showed that PA could combine well with the core targets. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis suggested that the PI3K/AKT signaling pathway was possible for treating GC with PA. The experiment results demonstrated that PA could decrease the survival rate of HGC-27 cells, halt the progression of the cell cycle, enhance cell apoptosis, control the PI3K/AKT signaling pathway to stimulate apoptosis, and impede cell growth.