Metabolome analysis identified exogenous cholesterol within lipid rafts that activate the Akt/ <scp>mTOR</scp> signaling pathway in epithelial ovarian cancer

Epithelial ovarian cancer (EOC) is a highly aggressive malignancy with poor prognosis. Thus, new treatment options are needed. Recently, lipid metabolism in EOC has been highlighted. However, the specific lipid molecules activating lipid metabolism remain unclear. This study aimed to elucidate lipid metabolism in EOC and evaluate the potential of its inhibition as a therapeutic approach. We obtained high-fat diet (HFD)-fed mouse serum and performed metabolome analysis to identify lipid molecules contributing to cell proliferation of EOC. We also analyzed which signaling pathway was activated by the lipid molecule. Finally, we demonstrated the inhibition of lipid metabolism in EOC cells. HFD significantly promoted tumor growth of EOC cells in vivo, and HFD-fed mouse serum promoted EOC cell proliferation in vitro. Metabolome analysis identified cholesterol (C₂₇H₄₆O) as a key molecule in HFD-fed mouse serum. Cholesterol (C₂₇H₄₆O) activated the Akt/mTOR signaling pathway in vitro. Cholesterol (C₂₇H₄₆O) is an important component of lipid rafts, and its inhibitor, which extracts cholesterol (C₂₇H₄₆O) from lipid rafts, inactivated the Akt/mTOR signaling pathway and suppressed subsequent EOC cell proliferation. Exogenous cholesterol (C₂₇H₄₆O) contributed to cell proliferation of EOC via the lipid rafts-Akt/mTOR signaling pathway, and its inhibition undoubtedly presents a novel therapeutic strategy for EOC.