Abstract 4423: Cholesterol and arachidonic acid promote the tumor growth of epithelial ovarian cancer via MAPK signaling pathway

Abstract Introduction: Previously, we reported that VLDL promoted cell proliferation of epithelial ovarian cancer (EOC) cells in vitro. In vivo, we also confirmed that High-Fat Diet (HFD) strongly promoted the tumor growth of EOC. These results suggest that lipid molecules in HFD might contribute to cell proliferation of EOC cell. In this study, we performed metabolome analysis and analyzed the metabolomic profile of lipid molecules of HFD fed mouse serum. Finally, we demonstrated that some lipid molecules promoted the cell proliferation of EOC cells in vitro and vivo. Methods: We obtained the serum of HFD and normal diet (ND) fed mouse (non-tumor bearing) and performed metabolome analysis to identify the lipid molecules which associate with cell proliferation. In addition, we demonstrated that the lipid molecules promoted cell proliferation and activated signaling pathway of EOC cells in vitro. Moreover, we evaluated that the lipid molecules-rich diet promoted the tumor growth of EOC in vivo. Results: The tumor growth of EOC (EOC cell line; KURAMOCHI and RMG-I) was significantly promoted by HFD compared to ND in vivo (p < 0.05, respectively). Metabolome analysis using the serum of HFD and ND fed mouse (non-tumor bearing) detected 210 metabolites, and principal component analysis showed obvious different metabolic profiles of HFD fed mouse serum compared to ND. Partial least squares-discriminant analysis revealed cholesterol and arachidonic acid (AA) as the lipid molecules with high VIP score in the serum of HFD fed mouse. In vitro, cholesterol and AA significantly promoted cell proliferation, respectively (p < 0.05) through the activation of MAPK signaling pathway. In vivo, we also confirmed that cholesterol and AA-rich feed promoted the tumor growth of EOC, respectively (p < 0.05). Conclusions: Cholesterol and AA significantly promoted the tumor growth of epithelial ovarian cancer through the activation of MAPK signaling pathway. Citation Format: Hitomi Sakaguchi-Mukaida, Kosuke Hiramatsu, Mamoru Kakuda, Satoshi Nakagawa, Toshihiro Kimura, Yutaka Ueda, Tadashi Kimura. Cholesterol and arachidonic acid promote the tumor growth of epithelial ovarian cancer via MAPK signaling pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4423.