Abstract
Abstract The present study investigated the effects of dietary supplementation with selenium (Se) on spontaneous metastasis of Lewis lung carcinoma (LLC) in mice fed a high-fat diet using a 2x2 design. Three-week-old male C57BL/6 mice were fed the AIN93G diet or that diet modified with 45% calories from fat supplemented with or without 2.5 mg Se/4029 kcal as methylseleninic acid for 6 weeks, at which time they were injected subcutaneously with 2.5x105 LLC cells. The resulting primary tumor was removed surgically 10 days later, and the experiment was terminated after an additional 10 days. Consumption of the high-fat diet significantly increased the body fat mass, regardless of Se supplementation, compared to the AIN93G diet (p<0.01). The high-fat diet increased lung metastases by 17% compared to the AIN93G diet (p<0.01). Selenium supplementation reduced the metastases by 11% compared to non-supplemented controls (p<0.05); however, the reduction was greater in AIN93G-fed mice (18%) than in mice fed the high-fat diet (5%). Supplemental Se reduced plasma concentrations of proteolytic proteases (uPA, p<0.01; MMP-9, p<0.05) and angiogenic factors (VEGF, p<0.01; TIMP-1, p<0.01) compared to non-supplemented controls. The high-fat diet significantly increased plasma concentrations of adipokines PAI-1, MCP-1, TNF-α and leptin regardless of the level of dietary Se; however, supplemental Se reduced plasma PAI-1 (p≤0.05) and MCP-1 (p≤0.05) in AIN93G-fed mice. These results demonstrate that consumption of a high-fat diet abrogated the anti-metastatic effects of Se, and that such an abrogation may involve adipose-derived inflammatory cytokines. Citation Format: Lin Yan. Consumption of a high-fat diet abrogates inhibitory effects of selenium on spontaneous metastasis of Lewis lung carcinoma in mice. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 245. doi:10.1158/1538-7445.AM2014-245
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