Changning Maternity and Infant Health Hospital, East China Normal University, Shanghai, China; Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Changning Maternity and Infant Health Hospital, East China Normal University, Shanghai, China.
J Pharm Biomed Anal. 2021 Feb 5;194:113763. doi: 10.1016/j.jpba.2020.113763. Epub 2020 Nov 20.
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.
花生四烯酸（AA）与乳腺癌密切相关。除了环加氧酶和脂加氧酶调节的两种代谢途径外，AA 还有第三种代谢途径，通过细胞色素 P450（CYP）酶产生羟二十碳四烯酸（HETE）和环氧二十碳三烯酸（EET）。AA 的靶向 CYP 介导途径不仅可以杀死癌细胞，还可以抑制肿瘤周围的间质微环境。因此，从 AA 代谢组中识别潜在的生物标志物来诊断和治疗乳腺癌是有意义的。本研究建立了一种液相色谱-串联质谱（LC-MS/MS）方法，用于分析 MMTV-PyMT 小鼠（一种自发性乳腺癌小鼠模型）中的 AA 及其主要代谢物 EET 和 HETE。结果表明，正常和 MMTV-PyMT 小鼠的血浆和肿瘤组织中 AA、12-HETE、19-HETE 和 8,9-EET 的浓度存在显著差异。因此，上述类二十烷酸可能可作为乳腺癌诊断的新生物标志物。本研究为乳腺癌的识别和诊断提供了新的视角。
