Department of Human Health and Nutritional Sciences, University of Guelph, Animal Science/Nutrition Building, Room 342, 491 Gordon Street, N1G 2W1 Guelph, ON, Canada.
Lipids Health Dis. 2014 Jun 11;13:96. doi: 10.1186/1476-511X-13-96.
Breast cancer is attributable to modifiable risk factors including the intake of dietary n-3 polyunsaturated fatty acids (PUFA). A key piece of evidence, yet to be addressed, that would demonstrate a causal relationship between n-3 PUFA and breast cancer, is a dose-dependent effect of n-3 PUFA on tumour outcomes. Thus, the objective of the present study was to determine whether n-3 PUFA reduces mammary gland tumor outcomes in a dose-dependent manner in female MMTV-neu(ndl)-YD5 transgenic mice, an aggressive model of human breast cancer.
Harems were provided one of three experimental diets comprised of 0, 3 or 9% (w/w) menhaden fish oil containing n-3 PUFA. Female offspring were weaned onto the same parental diet and maintained on their respective diet for 20 weeks. Tumour onset, size and multiplicity were measured throughout the study. Fatty acid composition of mammary gland and tumours were determined by gas-liquid chromatography.
Tumour size was significantly (p < 0.05) reduced in a dose-dependent manner. n-3 PUFA were also incorporated in a dose-dependent manner; differential incorporation was observed for eicosapentaenoic and docosapentaenoic acids into mammary gland tissue, while docosahexaenoic acid was preferentially incorporated into tumours.
Overall, the present study provides fundamental knowledge about the dose-dependent effect of n-3 PUFA on tumour outcomes in a pre-clinical model and also sheds light on the differential role of individual n-3 PUFA on tumour outcomes.
乳腺癌归因于可改变的风险因素，包括饮食中 n-3 多不饱和脂肪酸（PUFA）的摄入。尚未解决的一个关键证据是 n-3 PUFA 与乳腺癌之间存在因果关系，即 n-3 PUFA 对肿瘤结果的剂量依赖性影响。因此，本研究的目的是确定 n-3 PUFA 是否以剂量依赖的方式降低雌性 MMTV-neu(ndl)-YD5 转基因小鼠乳腺肿瘤的结果，该模型是人类乳腺癌的一种侵袭性模型。
将母鼠提供给三种实验饮食中的一种，这三种饮食分别含有 0、3 或 9%（w/w）的鲱鱼油，其中含有 n-3 PUFA。雌性后代断奶后开始食用相同的亲代饮食，并在各自的饮食中维持 20 周。在整个研究过程中测量肿瘤的发生、大小和多发性。通过气相色谱法测定乳腺和肿瘤的脂肪酸组成。
肿瘤大小呈剂量依赖性显著降低（p < 0.05）。n-3 PUFA 也呈剂量依赖性掺入；在乳腺组织中，二十碳五烯酸和二十二碳五烯酸的掺入存在差异，而二十二碳六烯酸优先掺入肿瘤。
总的来说，本研究为 n-3 PUFA 对临床前模型中肿瘤结果的剂量依赖性影响提供了基本的知识，也阐明了个体 n-3 PUFA 对肿瘤结果的不同作用。
