The Mechanism of Osthole in the Treatment of Gastric Cancer Based on Network Pharmacology and Molecular Docking Technology.

OBJECTIVE

To study the mechanism of osthole in GC based on network pharmacology and molecular docking.

METHODS

The potential targets of osthole were predicted through the TCM System Pharmacology Analysis Platform, SwissTargetPrediction, and PharmMapper database. Targets related to gastric cancer were obtained through OMIM and GeneCard database. The online tool Venny 2.1.0 was used to screen GC and common target of osthole. The targets after the intersection of drugs and diseases were entered into the STRING database, and the protein interaction network was constructed, and the core targets with high correlation were screened out. The WebGestalt website was used to GO functional enrichment and KEGG pathway analysis and visualization with KOBAS website. The Cytoscape 3.8.2 was employed to draw the C-T-P-D (compound-target-pathway-disease) network visualization diagram. Finally, molecular docking validation was performed using PyMOL 2.5 and Discovery Studio Standalone.

RESULTS

Through prediction and screening, 108 corresponding targets were screened from osthole, and 173 targets were obtained after intersecting with gastric cancer targets. Among them, the top ten targets were the core targets of this study, including MAPK3, MAPK1, SRC, AKT1, HSP90AA1, RXRA, ESR1, RELA, MAPK14, and EGFR. The analysis of GO, KEGG, and PPI showed that the mechanism of action of osthole against GC may be closely related to the regulation of the PI3K signaling pathway. The results of molecular docking showed that osthole had a good affinity with MAPK3, which is a crucial part of the PI3K signaling pathway.

CONCLUSION

This study preliminarily revealed the targets and related pathways of osthole in the treatment of gastric cancer and provided a new idea for further exploration of osthole targeted prevention and treatment of gastric cancer.