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膳食补充硒可调节脑转移瘤的生长并改变脑微血管中黏附分子的表达。

Dietary Selenium Supplementation Modulates Growth of Brain Metastatic Tumors and Changes the Expression of Adhesion Molecules in Brain Microvessels.

作者信息

Wrobel Jagoda K, Wolff Gretchen, Xiao Rijin, Power Ronan F, Toborek Michal

机构信息

Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.

Nutrigenomics Research Center, Alltech, Nicholasville, KY, 40356, USA.

出版信息

Biol Trace Elem Res. 2016 Aug;172(2):395-407. doi: 10.1007/s12011-015-0595-x. Epub 2015 Dec 26.

Abstract

Various dietary agents can modulate tumor invasiveness. The current study explored whether selenoglycoproteins (SeGPs) extracted from selenium-enriched yeast affect tumor cell homing and growth in the brain. Mice were fed diets enriched with specific SeGPs (SeGP40 or SeGP65, 1 mg/kg Se each), glycoproteins (GP40 or GP65, 0.2-0.3 mg/kg Se each) or a control diet (0.2-0.3 mg/kg Se) for 12 weeks. Then, murine Lewis lung carcinoma cells were infused into the brain circulation. Analyses were performed at early (48 h) and late stages (3 weeks) post tumor cell infusion. Imaging of tumor progression in the brain revealed that mice fed SeGP65-enriched diet displayed diminished metastatic tumor growth, fewer extravasating tumor cells and smaller metastatic lesions. While administration of tumor cells resulted in a significant upregulation of adhesion molecules in the early stage of tumor progression, overexpression of VCAM-1 (vascular call adhesion molecule-1) and ALCAM (activated leukocyte cell adhesion molecule) messenger RNA (mRNA) was diminished in SeGP65 supplemented mice. Additionally, mice fed SeGP65 showed decreased expression of acetylated NF-κB p65, 48 h post tumor cell infusion. The results indicate that tumor progression in the brain can be modulated by specific SeGPs. Selenium-containing compounds were more effective than their glycoprotein controls, implicating selenium as a potential negative regulator of metastatic process.

摘要

多种膳食因子可调节肿瘤侵袭性。本研究探讨了从富硒酵母中提取的硒糖蛋白(SeGPs)是否会影响肿瘤细胞在脑内的归巢和生长。给小鼠喂食富含特定硒糖蛋白(SeGP40或SeGP65,各含1 mg/kg硒)、糖蛋白(GP40或GP65,各含0.2 - 0.3 mg/kg硒)的饲料或对照饲料(0.2 - 0.3 mg/kg硒),持续12周。然后,将小鼠Lewis肺癌细胞注入脑循环。在肿瘤细胞注入后的早期(48小时)和晚期(3周)进行分析。脑内肿瘤进展的成像显示,喂食富含SeGP65饲料的小鼠转移性肿瘤生长减弱,渗出的肿瘤细胞减少,转移灶更小。虽然在肿瘤进展早期给予肿瘤细胞会导致黏附分子显著上调,但在补充SeGP65的小鼠中,血管细胞黏附分子-1(VCAM-1)和活化白细胞细胞黏附分子(ALCAM)信使核糖核酸(mRNA)的过表达减少。此外,喂食SeGP65的小鼠在肿瘤细胞注入后48小时,乙酰化核因子κB p65的表达降低。结果表明,特定的硒糖蛋白可调节脑内肿瘤进展。含硒化合物比其糖蛋白对照更有效,这表明硒可能是转移过程的潜在负调节因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59e/4930949/ccf4107c7d15/12011_2015_595_Fig1_HTML.jpg

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