Inhibiting cholesterol de novo synthesis promotes hepatocellular carcinoma progression by upregulating prostaglandin E synthase 2-mediated arachidonic acid metabolism under high fatty acid conditions.

ABSTRACT: Inhibition of cholesterol de novo synthesis (DNS) by statins has controversial effects on the treatment of hepatocellular carcinoma (HCC). High fatty acid conditions have been reported to limit the effect of statins on metabolism diseases. Whether high fatty acid conditions interfere with the effect of statins on HCC remains unclear. Here, we reported that inhibiting cholesterol DNS with atorvastatin promoted the oncogenic capabilities of diethylnitrosamine (DEN) in mice fed high fatty acid diets (HFD). The combined analysis of metabolomics and transcriptomics revealed that arachidonic acid (AA) metabolism was the most significant changed pathway between mice with and without atorvastatin treatment. In vitro, in the presence of AA precursor linoleic acid (LA), atorvastatin promoted the pro

SUBMITTER: Zhao Z 

PROVIDER: S-EPMC10859596 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature