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在携带乳腺肿瘤异种移植瘤的小鼠中补充酵母硒对促氧化-抗氧化活性和抗肿瘤作用的影响

Supplementation with Selenium yeast on the prooxidant-antioxidant activities and anti-tumor effects in breast tumor xenograft-bearing mice.

作者信息

Guo Chih-Hung, Hsia Simon, Hsiung Der-Yun, Chen Pei-Chung

机构信息

Institute of Biomedical Nutrition, Hung-Kuang University, Taichung, 433, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, 404, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung, 413, Taiwan; Taiwan Nutraceutical Association, Taipei 115, Taiwan.

Institute of Biomedical Nutrition, Hung-Kuang University, Taichung, 433, Taiwan; Taiwan Nutraceutical Association, Taipei 115, Taiwan.

出版信息

J Nutr Biochem. 2015 Dec;26(12):1568-79. doi: 10.1016/j.jnutbio.2015.07.028. Epub 2015 Aug 12.

Abstract

Selenium (Se) is essential for antioxidant activity involved in immune function and anti-carcinogenic action, whereas at higher concentrations, Se may have pro-oxidant properties. The present study was aimed at determining the effects of Se supplementation, as Se yeast, on oxidative stress in non-tumor/tumor tissues, as well as regulation of the apoptotic process, and immune responses in mice-bearing breast tumor xenografts. Female BALB/cByJNarl mice were divided into control (CNL and CNL-con), Se-supplemented control (CNL-HS, given as a single oral dose of 912 ng Se daily), breast tumor-bearing (TB and TB-con), TB-LS (228 ng Se), TB-MS (456 ng Se) and TB-HS (912 ng Se) groups. All mice were treated with/without Se for 14 days. A number of variables were further measured. Compared with the TB groups, tumor bearing mice with Se supplement had increased plasma Se concentrations, reduced erythrocyte Se-dependent glutathione peroxidase (GPx) activity and malondialdehyde (MDA) products and inhibited tumor growth. They have also higher Se concentrations in non-tumor and tumor tissues. Significantly elevated concentrations of MDA and reduced GPx activities, as well as increased anti-apoptotic bcl-2 and tumor suppressor p53 concentrations in tumor tissues were observed as Se accumulated in tumor, whereas lower MDA products were found in various non-tumor tissues than did the corresponding values. Further, there were elevated concentrations of Th1-derived cytokines and decreased Th2-type interleukin (IL)-4 in tumor-bearing mice with the treatment of Se. In conclusion, accumulation of Se in tumors may induce oxidative stress and p53-dependent pro-oxidative apoptosis, thus inhibiting the growth of breast tumor.

摘要

硒(Se)对于参与免疫功能和抗癌作用的抗氧化活性至关重要,而在较高浓度下,硒可能具有促氧化特性。本研究旨在确定补充硒酵母形式的硒对荷乳腺肿瘤异种移植小鼠的非肿瘤/肿瘤组织氧化应激、凋亡过程调节以及免疫反应的影响。将雌性BALB/cByJNarl小鼠分为对照组(CNL和CNL-con)、补充硒的对照组(CNL-HS,每日单次口服剂量为912 ng硒)、荷乳腺肿瘤组(TB和TB-con)、TB-LS(228 ng硒)、TB-MS(456 ng硒)和TB-HS(912 ng硒)组。所有小鼠接受或不接受硒处理14天。进一步测量了多个变量。与TB组相比,补充硒的荷瘤小鼠血浆硒浓度升高,红细胞硒依赖性谷胱甘肽过氧化物酶(GPx)活性和丙二醛(MDA)产物降低,肿瘤生长受到抑制。它们在非肿瘤和肿瘤组织中的硒浓度也更高。随着硒在肿瘤中积累,观察到肿瘤组织中MDA浓度显著升高、GPx活性降低,以及抗凋亡bcl-2和肿瘤抑制因子p53浓度增加,而在各种非肿瘤组织中发现的MDA产物低于相应值。此外,在接受硒处理的荷瘤小鼠中,Th1衍生细胞因子浓度升高,Th2型白细胞介素(IL)-4降低。总之,肿瘤中硒的积累可能诱导氧化应激和p53依赖性促氧化凋亡,从而抑制乳腺肿瘤的生长。

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