Mechanisms of Proliferation Inhibition by <i>Ganoderma lucidum</i> Spore Oil in Colorectal Cancer: GC-MS, network pharmacology and experimental validation

Abstract Colorectal cancer (CRC) remains a significant global health challenge, driving increased interest in the potential preventive effects of dietary bioactive components. Ganoderma lucidum spore oil (GSO) is a food-grade lipid extract rich in bioactive fatty acids and triterpenoid compounds, yet its mechanism of action against CRC from a food science perspective remains incompletely elucidated. This study employed an integrated approach combining gas chromatography-mass spectrometry (GC-MS) analysis, network pharmacology prediction, and in vitro validation to preliminarily elucidate the mechanism by which GSO inhibits CRC proliferation. GC-MS identified key lipophilic constituents, while network pharmacology analysis revealed the PPAR signalling pathway and lipid metabolism as central to GSO's potential effects. In vitro experiments confirmed that GSO significantly inhibited the proliferation of the human colon cancer cell line HCT116 in a dose-dependent manner. Mechanistically, GSO treatment simultaneously upregulated PPAR subtype expression (PPARA, PPARD, PPARG) at both the protein and mRNA levels, while downregulating key lipid transport (FABP1, FABP4) and inflammatory (PTGS1) mediators. Molecular docking further confirmed the high-affinity interactions between GSO's primary constituents (linoleic acid, oleic acid, ganoderic acid C) and these core targets. the findings suggest that GSO as a source of bioactive lipids may exert anti-colorectal cancer effects primarily through regulating PPAR signalling pathways and associated lipid metabolism. These findings indicated that as a source of bioactive lipids, GSO may exert its anti-colorectal cancer effects primarily through regulating the PPAR signalling pathway and associated lipid metabolism. This study provides scientific evidence supporting the consideration of GSO as a potential functional food ingredient for colorectal cancer prevention and dietary intervention.