Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
Int J Cancer. 2013 Nov;133(9):2054-64. doi: 10.1002/ijc.28224. Epub 2013 Jul 6.
The survival rate for breast cancer drops dramatically once the disease progresses to the metastatic stage. Selenium (Se) is an essential micronutrient credited with having high anticancer and chemopreventive properties. In our study, we investigated if dietary Se supplementation modified breast cancer development in vivo. Three diets supplemented with sodium selenite, methylseleninic acid (MSA) or selenomethionine (SeMet), as well as a Se-deficient and a Se-adequate diet were fed to mice before mammary gland inoculation of 4T1.2 cells. The primary tumor growth, the numbers of cancer cells present in lungs, hearts, livers, kidneys and femurs and several proinflammatory cytokines were measured. We found that inorganic selenite supplementation provided only short-term delay of tumor growth, whereas the two organic SeMet and MSA supplements provided more potent growth inhibition. These diets also affected cancer metastasis differently. Mice fed selenite developed the most extensive metastasis and had an increased incidence of kidney and bone metastasis. On the other hand, mice fed the SeMet diet showed the least amount of cancer growth at metastatic sites. The MSA diet also provided some protection against breast cancer metastasis although the effects were less significant than those of SeMet. The cytokine profiles indicated that serum levels of interlukin-2, interleukin-6, interferon γ and vascular endothelial growth factor were elevated in SeMet-supplemented mice. There was no significant difference in tumor growth and the patterns of metastasis between the Se-deficient and Se-adequate groups. Our data suggest that organic Se supplementation may reduce/delay breast cancer metastasis, while selenite may exacerbate it.
一旦乳腺癌发展到转移阶段,其存活率会急剧下降。硒(Se)是一种必需的微量营养素,具有很高的抗癌和化学预防特性。在我们的研究中,我们研究了饮食中补充硒是否会改变体内乳腺癌的发展。在乳腺接种 4T1.2 细胞之前,用含有亚硒酸钠、甲基硒酸(MSA)或硒代蛋氨酸(SeMet)的三种饮食以及硒缺乏和硒充足的饮食对小鼠进行补充。测量了原发肿瘤的生长、肺部、心脏、肝脏、肾脏和股骨中存在的癌细胞数量以及几种促炎细胞因子。我们发现,无机硒补充剂仅提供了肿瘤生长的短期延迟,而两种有机硒代蛋氨酸和 MSA 补充剂则提供了更有效的生长抑制作用。这些饮食对癌症转移的影响也不同。喂食亚硒酸钠的小鼠发生了最广泛的转移,并且肾脏和骨骼转移的发生率增加。另一方面,喂食 SeMet 饮食的小鼠在转移部位的癌症生长最少。MSA 饮食也提供了一些对乳腺癌转移的保护作用,尽管效果不如 SeMet 明显。细胞因子谱表明,血清中白细胞介素-2、白细胞介素-6、干扰素 γ 和血管内皮生长因子的水平在 SeMet 补充的小鼠中升高。硒缺乏和硒充足组之间在肿瘤生长和转移模式方面没有显着差异。我们的数据表明,有机硒补充可能会减少/延迟乳腺癌转移,而亚硒酸盐可能会加剧这种情况。