Introduction Lipid metabolism and epithelial ovarian cacner (EOC) is strongly related in cell proliferation. In our preliminary experiment, High-Fat Diet (HFD) promoted tumor growth of EOC in vivo, however, it is unclear which lipid molecules contribute cell proliferation. In this study, we analyzed the metabolomic profile of HFD mouse serum by the metabolome and identified lipid molecules which promote tumor growth of EOC.

Methods We performed the metabolome using the serum of non-tumor bearing mouse fed with HFD or normal diet (ND) and compared metabolic profile. Moreover, we investigated which signaling pathways is activated by the identified lipid molecules in HFD mouse serum in vitro and in vivo.

Results The tumor growth of EOC was significantly promoted by HFD in vivo (p<0.05) and HFD serum also significantly proliferated EOC cells in vitro (p<0.05). We performed the metabolome using HFD and ND mouse serum and identified over 200 metabolites. PCA showed obvious different metabolic profiles of HFD serum compared to ND serum. Partial least squares-discriminant analysis revealed cholesterol and arachidonic acid (AA) as the lipid molecules abundant in HFD serum. Cholesterol and AA significantly promoted cell proliferation in vitro through the activation of Akt and MAPK signaling pathway, respectively (p<0.05). Finally, in vivo, we confirmed cholesterol and AA promoted the tumor growth of EOC, respectively (p<0.05).

Conclusion/Implications Cholesterol and AA activates Akt and MAPK pathway and promote cell proliferation/tumor growth of EOC.