TMET-03. STEAROYL-COA DESATURASE INHIBITOR SUPPRESSES IDH MUTANT GLIOMA GROWTH VIA ENHANCING LIPOLYSIS

Abstract BACKGROUND Mutant isocitrate dehydrogenase (IDH) produces 2-hydroxyglutarate (D2HG) and causes metabolic reprograming, but so far, little is known about the role of mutant IDH D2HG in de novo lipogenesis fatty acids synthesis. In this study, to develop a feasible drug for glioma, we targeted Stearoyl-CoA desaturase 1 (SCD1) catalyzing biosynthesis monosaturated (MUFA) suppress glioma progression. Materials METHODS We prepared genetically engineered cell lines (U251 wild type: U251WT U251 IDHR132H mutant: U251RH), normal human astrocytes (empty vector induced-NHA: NHAEV NHARH) patient derived lines. Lipid analysis was conducted by using LC-MS, functional SCD1 expression investigated RNA sequence Western-blotting. RESULTS LC-MS extracted Endoplasmic Reticulum revealed that there significantly higher amount MUFA than type. increased compared type due D2HG-mediated upregulation mutant. Therefore, which level indicated high sensitivity SCD inhibitor, apoptosis highly induced sequencing performed U251RH treated with inhibitor DMSO, lipid droplet metabolism-associated changed inhibitor-treated U251RH. Based on data, checked presence or absence lipolysis treatment, suggesting inhibition associated via enhanced mechanism. CONCLUSIONS produced directly induces enhances suggests would be glioma-specific treatment strategy.