DDRE-08. POTENTIAL THERAPEUTIC EFFECTS OF ETOMOXIR IN COMBINATION WITH TEMOZOLOMIDE AGAINST HUMAN GLIOBLASTOMA TUMORSPHERES. (9th November 2020)

• Record Type: Journal Article
• Authors: Hyun Kim, Eui; Shim, Jin-Kyoung; Park, Jungseong; Seon, Jieun; Kim, Hyun Sil; Moon, Ju Hyung; Chang, Jong Hee; Yook, Jong In; Kang, Seok-Gu
• Is Part Of: Neuro-oncology. Volume 22(2020)Supplement 2
• Page Start: ii62
• Page End: ii63
• Publication Date: 2020-11-09
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noaa215.253
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: PURPOSE: Glioblastoma (GBM) is the most common and lethal brain tumor with the median survival between 10 and 14 months. Since current treatments including surgical resection, radiation and chemotherapy fail to cure GBM, a new strategy to maximize the efficacy is needed. Here, etomoxir, an inhibitor of fatty acid oxidation, has been combined with temozolomide, a standard treatment for GBM, to examine its anti-tumor effects. Etomoxir has shown anti-cancer effects against human bladder, prostate cancers as well as GBM. We hypothesize that etomoxir inhibits fatty acid metabolism in cancer cell to suppress tumor progression while temozolomide causes cancer cell death. METHOD: Four kinds of human GBM tumorspheres (TSs) were treated with temozolomide or etomoxir alone, or in combination with each other. Therapeutic effects of two drugs were evaluated by measuring cell viability, apoptosis, neurosphere formation, 3D-invasion using collagen/matrigel matrix, and LC/MS analysis of energy metabolism. Protein and mRNA expression profiles after drug treatment were evaluated by western blotting and RNA-sequencing. RESULTS: Combination treatment of temozolomide and etomoxir significantly inhibited the cell viability, stemness, and invasiveness in GBM TSs. Expression levels of stemness-, invasiveness-associated markers were also decreased by the combined treatment. The combined treatment also significantly inhibited ATP production in TCA cycle. CONCLUSIONS: Our findings suggest that combined treatment of etomoxir and TMZ may be therapeutically effective in the treatment GBM