4.6 Article

Investigation of the content differences of arachidonic acid metabolites in a mouse model of breast cancer by using LC-MS/MS

出版社

ELSEVIER
DOI: 10.1016/j.jpba.2020.113763

关键词

Arachidonic acid (AA); Breast cancer; Cytochrome P450; LC-MS/MS; Biomarker

资金

  1. National Natural Science Foundation of China [81301908]
  2. Science and Technology Commission of Shanghai Municipality [18430760400]
  3. ECNU Multifunctional Platform for Innovation [011]

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Arachidonic acid plays a crucial role in breast cancer, and its metabolic pathways have the potential to kill cancer cells and inhibit the tumor microenvironment. By analyzing the concentrations of AA and its main metabolites in a breast cancer mouse model, new biomarkers for breast cancer diagnosis may be identified.
Arachidonic acid (AA) is closely associated with breast cancer. In addition to the two metabolic pathways regulated by cyclooxygenase and lipoxygenase, AA has a third metabolic pathway through which cytochrome P450 (CYP) enzymes produce hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs). The targeted CYP-mediated pathway of AA can not only kill cancer cells but also inhibit the interstitial microenvironment around a tumor. Therefore, it makes sense to identify potential biomarkers from the AA metabolome for the diagnosis and treatment of breast cancer. This study established a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the analysis of AA and its main metabolites, EETs and HETEs, in MMTV-PyMT mice, a spontaneous breast cancer mouse model. The results showed that there were significant differences in the concentrations of AA, 12-HETE, 19-HETE and 8,9-EET in plasma and tumor tissues between normal and MMTV-PyMT mice. Therefore, the eicosanoids mentioned above may be used as new biomarkers for breast cancer diagnosis. This study provides a new perspective for the recognition and diagnosis of breast cancer. (C) 2020 Elsevier B.V. All rights reserved.

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