Data from A New Model to Study the Role of Arachidonic Acid in Colon Cancer Pathophysiology

作者：Yang‐Yi Fan, Evelyn Callaway, Jennifer M. Monk, Jennifer S. Goldsby, Peiying Yang, Logan Vincent, Robert S. Chapkin · 年份：2023 · DOI：10.1158/1940-6207.c.6547582.v1 · 研究领域：Inflammatory mediators and NSAID effects、Cancer, Lipids, and Metabolism、Eicosanoids and Hypertension Pharmacology

<div>AbstractA significant increase in cyclooxygenase 2 (COX2) gene expression has been shown to promote cylcooxygenase-dependent colon cancer development. Controversy associated with the role of COX2 inhibitors indicates that additional work is needed to elucidate the effects of arachidonic acid (AA)-derived (cyclooxygenase and lipoxygenase) eicosanoids in cancer initiation, progression, and metastasis. We have recently developed a novel Fads1 knockout mouse model that allows for the investigation of AA-dependent eicosanoid deficiency without the complication of essential fatty acid deficiency. Interestingly, the survival rate of Fads1-null mice is severely compromised after 2 months on a semi-purified AA-free diet, which precludes long-term chemoprevention studies. Therefore, in this study, dietary AA levels were titrated to determine the minimal level required for survival, while maintaining a distinct AA-deficient phenotype. Null mice supplemented with AA (0.1%, 0.4%, 0.6%, 2.0%, w/w) in the diet exhibited a dose-dependent increase (P < 0.05) in AA, PGE2, 6-keto PGF1α, TXB2, and EdU-positive proliferative cells in the colon. In subsequent experiments, null mice supplemented with 0.6% AA diet were injected with a colon-specific carcinogen (azoxymethane) in order to assess cancer susceptibility. Null mice exhibited significantly (&l...