Prevention of ovarian cancer is the best approach for reducing the impact of this deadly disease. The laying hen is a robust model of spontaneous ovarian cancer that recapitulates the human disease. Dietary intervention with flaxseed, the richest vegetable source of omega-3 fatty acids (OM-3FAs) and phytoestrogen lignans, demonstrate the potential for effective prevention and amelioration of ovarian cancer by targeting inflammatory prostaglandin pathways. Prostaglandin E2 (PGE2) is the most pro-inflammatory ecoisanoid and one of the downstream products of two isoforms of cyclooxygenase (COX) enzymes: COX-1 and COX-2. Our objective was to investigate the effect of flaxseed supplementation for one year on ovarian cancer and correlate its effects to expression of COX enzymes and concentrations of prostaglandins. White Leghorn hens were fed 10% flaxseed-enriched or standard diet for one year. The severity of ovarian cancer was determined by gross pathology and histology. COX-1 and COX-2 localization and protein and mRNA expression and PGE2 and PGE3 concentrations in ovaries were measured by IHC, western blot, quantitative real-time PCR and LC-MS-MS, respectively. The results demonstrated a significant reduction in late stage ovarian tumors in the flaxseed-fed hens compared with the control diet-fed hens. In correlation with decreased ovarian cancer severity, concentrations of PGE2 and expression of COX-2 were diminished in ovaries of flaxseed-fed hens. PGE3 concentrations were below the level of detection. The results demonstrated that in normal ovaries, COX-1 was localized to the granulosa cell layer surrounding the follicles and ovarian surface epithelium (OSE) whereas COX-2 protein was localized to the granulosa cell layer in the follicle. Extensive COX-1 and COX-2 protein expression was found throughout the ovarian carcinoma. Our findings suggest that the flaxseed-mediated reduction in the severity of ovarian cancer in hens is correlated to the reduction in PGE2 in the ovaries of flaxseed-fed hens. These findings may provide the basis for clinical trials of dietary intervention targeting prostaglandin biosynthesis for the prevention and treatment of ovarian cancer.

译文

:预防卵巢癌是减少这种致命疾病影响的最佳方法。产蛋鸡是自发性卵巢癌的有力模型,可概括人类疾病。亚麻籽的膳食干预(omega-3脂肪酸(OM-3FAs)和植物雌激素木脂素的最丰富的植物来源)通过靶向炎症性前列腺素途径,证明了有效预防和改善卵巢癌的潜力。前列腺素E2(PGE2)是最易炎症的类二十烷酸,是环氧合酶(COX-1)和COX-2两种同工型的下游产物之一。我们的目标是研究亚麻籽对卵巢癌一年的治疗作用,并将其与COX酶的表达和前列腺素的浓度相关联。白来回鸡只母鸡饲喂10%亚麻籽或标准饮食,为期一年。卵巢癌的严重程度由总体病理学和组织学确定。通过IHC,蛋白质印迹,实时荧光定量PCR和LC-MS-MS分别检测卵巢中COX-1和COX-2的定位以及蛋白质和mRNA的表达以及PGE2和PGE3的浓度。结果表明,与对照饮食饲喂的母鸡相比,亚麻饲喂母鸡的晚期卵巢肿瘤显着减少。与卵巢癌严重程度降低相关,亚麻籽母鸡卵巢中的PGE2浓度和COX-2的表达降低。 PGE3浓度低于检测水平。结果表明,在正常卵巢中,COX-1位于卵泡和卵巢表面上皮(OSE)周围的颗粒细胞层,而COX-2蛋白则位于卵泡中的颗粒细胞层。在整个卵巢癌中发现了广泛的COX-1和COX-2蛋白表达。我们的发现表明,亚麻籽介导的母鸡卵巢癌严重程度的降低与亚麻籽母鸡卵巢中PGE2的降低有关。这些发现可为针对前列腺素生物合成的预防和治疗卵巢癌的饮食干预临床试验提供依据。

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