The antitumor efficacy of Ganoderma lucidum spore oil in hepatoma H22-bearing mice depends on modulating immunity and inhibiting eicosanoid metabolism pathway in tumor cells

Ganoderma lucidum spore oil (GLSO) is a well-known dietary supplement that is beneficial for immuno-enhancement. Based on the close correlation between tumor occurrence and immunity. The immuno-enhancement ability of GLSO in hepatoma H22-bearing mice was investigated in this study, and our work aimed to reveal the potential mechanisms of the antitumor efficacy of GLSO. The GLSO components were identified via UHPLC-Q-Orbitrap HRMS. A H22 cell subcutaneously transplanted tumor mouse model was constructed, and GLSO was preadministered. The antitumor efficacy of GLSO in hepatoma H22-bearing mice was evaluated according to tumor size, tumor growth curves, tumor inhibition rates and Ki67 expression level. T and B lymphocyte proliferation, delayed hypersensitivity, NK cell killing activity, macrophage phagocytotic activity, cytokine levels and CD69 molecule expression were detected to estimate immune function. Flow cytometry and Pro-DIA quantitative proteomics analysis were performed to investigate the potential mechanism of GLSO in tumor inhibition, which was verified by WB and RT-PCR. Thirty-eight compounds including triterpenoids, fatty acids and esters, were identified from GLSO. GLSO treatment prevented tumor occurrence and inhibited tumor growth because of the smaller initial and final tumor volumes and lower Ki67 expression. Treatment with GLSO promoted a strong immune response in hepatoma H22-bearing mice and improved tumor immune microenvironment. Proteomics analysis showed that GLSO inhibited eicosanoid metabolism pathway, WB and RT-PCR re-check these results. In conclusion, these findings support that GLSO prevents the occurrence of tumor depending on its immunomodulatory effects and we first report that GLSO restricts tumor growth by inhibiting eicosanoid metabolism pathway.