Abstract

Abstract Available evidence indicates that diets enriched in the ratio of n-3 fatty acids or dietary energy restriction (DER) have a broad range of health-related benefit including prevention of breast cancer. However, the number of studies in the combined effects of these intervention strategies have been investigated is limited. The objective of this investigation was to determine the effect of the combination of dietary n-3 and DER on mammary carcinogenesis, on plasma levels of cancer associated growth factors and cytokines and on molecular regulators in mammary carcinomas using a pre-clinical rat model for breast cancer. Female Sprague Dawley rats were injected with 1-methyl-1-nitrosourea (50 mg/kg) and 7 days thereafter randomized to four groups (n=30/group), 1) control (dietary n-6/n-3=1:1); 2) high n-3 (dietary n-6/n-3=1:10); 3) 20%DER (dietary n-6/n-3=1:1); 4) high n-3 + 20%DER (dietary n-6/n-3=1:10). Rats were fed a modification of the AIN-93G diet formulation that contained 30% of dietary calories from fat (currently recommended in the US Dietary guidelines). It was observed that mammary cancer incidence, cancer multiplicity and tumor burden were reduced and cancer latency was elongated for the rats in groups 2-4 compared to the rats in group 1, and the significant differences were observed between group 1 (n-6/n-3=1:1) and 4 (n-6/n-3=1:10 + 20%DER). The protective dietary combination of high n-3 and DER was associated with significant reductions in plasma IGF-1, insulin, and leptin and increased adiponectin compared to rats fed the control diet (n-6/n-3=1:1, p<0.01). Carcinomas induced in the protected animals were smaller in mass with altered levels of proteins in the PPAR and mTOR pathways on which plasma insulin had the most impact. This work was supported by grant KG081632 from the Susan G. Komen Foundation. Citation Format: Weiqin Jiang, Zongjian Zhu, John N. McGinley, Andrea Manni, Henry J. Thompson. Effect of omega-3 fatty acid and dietary energy restriction on mammary carcinogenesis, circulating biomarkers and molecular regulators in rats. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 193. doi:10.1158/1538-7445.AM2013-193

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