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Pro DIA-quantitative proteomics analysis reveals the mechanism of ganoderma lucidum spore oil suppressing tumor growth in hepatoma H22-bearing mice

ABSTRACT: Ganoderma lucidum spore oil (GLSO) is a well-known dietary supplement that is beneficial for immunoenhancement and shows good antitumor efficacy. However, the anti-tumor mechanism of GLSO remains unclear. Three tumor samples were randomly taken from model group mice and H-GLSO group mice, and the experimental operations were performed. The results revealed that 340 proteins were upregulated and 599 proteins were downregulated after treatment with GLSO . WikiPathway enrichment analysis of the differentially expressed proteins revealed that the lipoxygenase (LOX), cyclooxygenase (COX) and cytochrome P450 (P450) mediated eicosanoid metabolism pathways in tumor tissues were significantly inhibited after treatment with GLSO. Further statistical analysis of the differentially expressed proteins in the eicosanoid metabolism pathway was conducted to visualize the relevant results. The results showed that after intervention with GLSO, key proteins of the eicosanoid metabolism pathway, including the Gpx1, Lta4h, Ephx2, Alox15, Alox5, Ptgr1, Cyp4f3, Cyp4f14, Ggt5, Acox3, Ptgs1, Tbxas1, Pla2g4a, and Cyp2j5 were significantly downregulated in the tumor tissues of hepatoma H22-bearing mice treated with GLSO.

ORGANISM(S): Mus Musculus

SUBMITTER: Qing Wang

PROVIDER: PXD062448 | iProX | Tue Apr 01 00:00:00 BST 2025

REPOSITORIES: iProX

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2005-07-16 | GSE2362 | GEO

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Project description:NADPH-cytochrome P450 reductase (CPR) is important for the functions of many enzymes, such as microsomal cytochrome P450 (P450) monooxygenases and heme oxygenases. Two mouse models with deficient CPR expression in adults were recently generated in this laboratory: liver-Cpr-null (with liver-specific Cpr deletion) (Gu et al., J. Biol. Chem., 278, 25895-25901, 2003) and Cpr-low (with reduced CPR expression in all organs examined) (Wu et al. J. Pharmacol. Expt. Ther. 312, 35-43, 2005). The phenotypes included a reduced serum cholesterol level and an induction of hepatic P450 in both models, and hepatomegaly and fatty liver in the liver-Cpr-null mouse alone. Our aim was to identify hepatic gene-expression changes related to these phenotypes. Cpr-lox mice, which have normal CPR expression (Wu et al., Genesis, 36, 177-181, 2003.), were used as the control in microarray analysis. A detailed analysis of the gene-expression changes in lipid metabolism and transport pathways revealed potential mechanisms, such as an increased activation of constitutive androstane receptor (CAR) and a decreased activation of peroxisomal proliferators activated receptor alpha (PPARï?¡) by precursors of cholesterol biosynthesis, that underlie common changes (e.g., induction of multiple P450s and inhibition of genes for fatty acids metabolism) in response to CPR-loss in the two mouse models. Moreover, we also uncovered model-specific gene-expression changes, such as the induction of a lipid translocase (CD36 antigen) and the suppression of carnitine O-palmitoyltransferase 1 (CPT1a) and acyl-CoA synthetase long-chain family member 1 (Acsl1), that are potentially responsible for the severe hepatic lipidosis observed in liver-Cpr-null, but not Cpr-low mice.

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