Abstract 283: Cholesterol(C27H46O)identified by metabolomics enhance lipid raft composition for cell proliferation in epithelial ovarian cancer

Abstract Objective: We previously reported that lipoprotein promoted cell proliferation of epithelial ovarian cancer (EOC) cells in vitro. Moreover, we demonstrated High-Fat Diet (HFD) strongly promoted the tumor growth of EOC in vivo and HFD mouse serum promoted cell proliferation in vitro. These results suggest that lipid molecules derived from HFD contribute to cell proliferation of EOC. In this study, we aimed to identify the lipid molecules in HFD mouse serum which contribute to cell proliferation of EOC cells by metabolomics and figure out the function of the lipid molecule. Methods: We obtained serum of HFD and normal diet (ND) fed mouse and performed metabolomics to identify the lipid molecules which contribute to cell proliferation of EOC. In vitro, we validated that lipid molecules in HFD mouse serum promote the cell proliferation and analyzed which signaling pathway was activated. In vivo, we evaluated the effect of lipid molecules-rich diet in tumor growth. We also evaluate the association of lipid molecules and lipid rafts in EOC cells. Results: HFD significantly promoted the tumor growth EOC in vivo (p < 0.05), and HFD mouse serum also promoted cell proliferation of EOC cells in vitro (p < 0.05). Metabolomics showed obvious different metabolic profiles of HFD and ND mouse serum (non-tumor bearing). Partial least squares-discriminant analysis revealed that cholesterol (C27H46O) ranked highest as the lipid molecule in HFD mouse serum. In vitro, cholesterol significantly promoted cell proliferation (p < 0.05) via Akt/mTOR signaling pathway. Moreover, we demonstrated that cholesterol-rich diet promoted the tumor growth of EOC (p < 0.05). Finally, we evaluated that lipid raft inhibitor blocked cholesterol induced cell proliferation (p < 0.05). Conclusions: Cholesterol (C27H46O) uptake lead to the cell proliferation of epithelial ovarian cancer via stimulation Akt/mTOR signaling pathway following lipid raft. Citation Format: Hitomi Sakaguchi-Mukaida, Kosuke Hiramatsu, Tatsuo Masuda, Mamoru Kakuda, Satoshi Nakagawa, Tadashi Iwamiya, Shinya Matsuzaki, Yutaka Ueda. Cholesterol(C27H46O)identified by metabolomics enhance lipid raft composition for cell proliferation in epithelial ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 283.