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979 Cholesterol and arachidonic acid in high-fat diet promotes the tumor growth of epithelial ovarian cancer via MAPK signaling pathway
  1. Kosuke Hiramatsu,
  2. Mamoru Kakuda,
  3. Satoshi Nakagawa,
  4. Toshihiro Kimura,
  5. Yutaka Ueda and
  6. Tadashi Kimura
  1. Osaka University, Suita, Japan


Introduction/Background Previously, we reported that VLDL promoted cell proliferation of epithelial ovarian cancer (EOC) cells in vitro. In vivo, we also demonstrated that High-Fat Diet (HFD) strongly promoted the tumor growth of EOC than Normal-Diet (ND). These results suggest that lipid molecules in HFD might contribute to cell proliferation of EOC. 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 cell proliferation of EOC cells in vitro and vivo.

Methodology We obtained the serum of HFD and ND fed mouse (non-tumor bearing) and performed metabolome analysis to identify the lipid molecules which associate with cell proliferation. At first, we compared the cell proliferative effects with using each serum. Second, we demonstrated that the lipid molecules promoted cell proliferation and activated signaling pathway of EOC cells in vitro. In addition, we evaluated the tumor progression by lipid molecules in vivo.

Results The tumor growth of EOC 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, we demonstrated HFD serum promoted the cell proliferation compared to ND serum (p < 0.05, respectively). We also detected cholesterol and AA significantly promoted cell proliferation through MAPK signaling pathway.

In vivo, we also confirmed that cholesterol and AA promoted the tumor growth.

Conclusion Cholesterol and AA significantly promoted the tumor growth of epithelial ovarian cancer through the activation of MAPK signaling pathway.

Disclosures No COI.

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