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
Gastric cancer (GC) is one of the most serious malignant tumors of the digestive tract, with high morbidity and mortality. In recent years, more and more evidence has shown that natural ingredients from traditional Chinese medicine can prevent and inhibit the occurrence and development of GC, showing great therapeutic potential.
Network pharmacology is used to predict the targets and pathways of drugs in the treatment of diseases, and the method of experimental verification is used to verify them, which provides an effective reference for further elucidating the molecular mechanism of natural products in the treatment of GC.
To find the possible targets and pathways of pachymic acid (PA) in the treatment of GC, and to explore the molecular mechanism of PA promoting apoptosis and arresting cell cycle of GC cells by regulating PI3K/AKT signal transduction.
Using the TCMSP database to find the components of Poria cocos, we identified PA in Poria cocos as a potential effective component in the treatment of GC. The PharmMapper database was used to find the related targets of PA, and the GENECARDS and OMIM databases were used to find the related targets of GC, and the common targets were found by intersection. The protein-protein interaction network was constructed, and the top five core targets were screened according to the degree value. The Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis were used to identify related pathways. Molecular docking and clinical correlation studies were used to explore the effects of core targets on GC. Cell Counting Kit-8, colony formation assay and flow cytometry were used to detect cell function indexes. Western blot was used to determine the effect of PA on PI3K/AKT signaling pathway and apoptosis pathway.
A total of 217 possible targets of PA in the treatment of GC were identified by network pharmacology, and the top five core targets were found: Proto-oncogene tyrosine-protein kinase Src, mitogen-activated protein kinase 1, phosphatidylinositol 3-kinase regulatory subunit alpha, heat shock protein 90-alpha, tyrosine-protein phosphatase non-receptor type 11. KEGG pathway analysis showed that PI3K/AKT signaling pathway was a possible pathway for the treatment of GC. Molecular docking results showed that the binding energy between PA and PI3KR1 was the highest (-8.8 kcal/mol). Experiments on HGC-27 cells confirmed that PA could inhibit the proliferation of GC cells, promote the apoptosis of cells and arrest their G0/G1 phase. Western blot results showed that PA decreased the expression of phosphorylated PI3K and AKT in GC cells, and also had an effect on apoptosis-related proteins.
The inhibitory effect of PA on GC proliferation and its potential to induce apoptosis of GC cells were confirmed by network pharmacological analysis and experimental verification.
PA have shown high efficiency and low toxicity in the treatment of GC. However, PA have not been truly developed into relevant drugs for clinical trials, and there is still a long way to go for the application of PA in the clinical treatment of GC. In the future, we look forward to making the treatment of GC more in-depth through more studies on the effectiveness of PA on GC and providing more treatment options for patients with GC.