Exploration of the role of Fomitopsis officinalis Ames in the treatment of gastric cancer using network pharmacology, molecular docking, and in vitro experiments.

Abstract

Background: Gastric cancer (GC) is one of the most common malignant tumors worldwide, with approximately one million people diagnosed with gastric cancer each year. Although the incidence and mortality rates of gastric cancer have decreased in recent years, it remains the third leading cause of cancer-related deaths globally. Fomes officinalis Ames (FOA), also known as A LI HONG or deciduous matsutake, the dried fruiting body of medicinal polypore fungus belongs to the Polyporaceae family. It is traditionally used in Chinese medicine to relieve coughs and asthma, dispelling wind and dampness, reducing swelling, and alleviating pain. However, the role of FOA in the treatment of gastric cancer remains unknown. This study systematically elaborates on the therapeutic effect of FOA triterpenic acids on human gastric cancer MKN-45 cells, providing a theoretical basis for their development as natural-sourced anti-tumor drugs. Future research could further explore their molecular targets, tap into the application value of FOA triterpenic acids in the comprehensive treatment of GC, and offer new strategies for the integrated traditional Chinese and Western medicine treatment of GC.

Methods: In this study, a network pharmacology approach was employed to identify relevant targets from drug and disease-related databases. The five active components of FOA were retrieved from the Swiss Target Prediction (http://www.swisstargetprediction.ch/) database, and 379 drug active component targets were predicted. A total of 14,092 gastric cancer targets were retrieved from the GeneCards (https://www.genecards.org/) database using the keyword "gastric cancer". Venny 2.1 was used to analyze the intersections, and a protein-protein interaction (PPI) network was constructed. The PPI network contains 328 nodes and 4,486 edges. Core targets were visualized and analyzed using Cytoscape software. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to elucidate the associated biological functions and signaling pathways. Meanwhile, molecular docking of core targets with the main chemical components of FOA was performed using AutoDock software. Finally, in vitro experiments were conducted using human gastric cancer MKN-45 cells to validate the findings.

Results: Network pharmacology and molecular docking studies have shown that the triterpenic acid components in FOA exhibit strong molecular binding affinity with the core targets CASP3 and EGFR. They also predict that FOA may exert anti-gastric cancer effects by regulating pathways such as neuroactive ligand-receptor interaction and cancer-related pathways. Additionally, a method for extracting and purifying FOA triterpenic acids was successfully established, with its methodological validation meeting the required standards; chromatographic peaks of triterpenic acid indicator components were observed at the corresponding retention times (4.37 min, 16.71 min). In vitro experiments demonstrated that Fomitopsis officinalis polysaccharides and triterpenic acids could significantly inhibit the proliferation of gastric cancer cells. The IC50 after 24 h and 48 h of treatment were 41.26 μg/mL and 16.21 μg/mL, respectively. These components arrested the gastric cancer cell cycle at the G1, inhibited cell migration and invasion, and induced cell apoptosis by activating CASP3. All these findings further highlight the potential application value of FOA in gastric cancer treatment.