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多糖通过调控 Wnt/β-连环蛋白通路和改变血清内源性代谢物抑制 1-甲基-2-硝基-1-亚硝基胍诱导的大鼠胃癌癌前病变。

Polysaccharides Inhibit 1-Methyl-2-Nitro-1-Nitrosoguanidine Induced Precancerous Lesions of Gastric Cancer in Rats through Regulating Wnt/β-Catenin Pathway and Altering Serum Endogenous Metabolites.

机构信息

Research Center for Differentiation and Development of Basic Theory of Traditional Chinese Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.

Jiangxi Province Key Laboratory of TCM Etiopathogenisis, Nanchang 330004, China.

出版信息

Molecules. 2019 Jul 23;24(14):2660. doi: 10.3390/molecules24142660.

DOI:10.3390/molecules24142660
PMID:31340453
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6680496/
Abstract

is a herb in traditional Chinese medicine where polysaccharides (DOP) are the main active ingredient. This study aimed at evaluating DOP efficiency at inhibiting 1-Methyl-2-nitro-1-nitrosoguanidine (MNNG) induced precancerous lesions of gastric cancer (PLGC) in rats through the Wnt/b-catenin pathway and analyzing the variations of serum endogenous metabolites. PLGC was established in male Sprague-Dawley (SD) rats by administering 150 μg/mL MNNG in drinking water for 7 months and giving 0.1 mL of 10% NaCl once weekly during the initial 20 weeks. Treatment with DOP inhibited the progress of PLGC through decreasing the expression of β-catenin by immunohistochemical analysis. The futher study indicated DOP downregulated gene expression of Wnt2β, Gsk3β, PCNA, CyclinD1, and β-catenin, as well as protein expression of Wnt2β, PCNA, and β-catenin. On the other hand, there were nine endogenous metabolites identified after the DOP treatment. Among these, the most significant one is betaine because of its strong antioxidant activity, leading to an anti-tumor effect. DOP can inhibit MNNG-induced PLGC models via regulating Wnt/β-catenin pathway and by changing endogenous metabolites.

摘要

是一种中药,其中多糖(DOP)是主要的活性成分。本研究旨在通过 Wnt/β-连环蛋白通路评估 DOP 抑制 1-甲基-2-硝基-1-亚硝胍(MNNG)诱导的大鼠胃癌前病变(PLGC)的效率,并分析血清内源性代谢物的变化。通过给予雄性 Sprague-Dawley(SD)大鼠 150μg/mL MNNG 饮用水 7 个月,并在最初的 20 周内每周给予 0.1mL 10%NaCl,建立 PLGC。免疫组织化学分析表明,DOP 通过抑制β-连环蛋白的表达来抑制 PLGC 的进展。进一步的研究表明,DOP 下调了 Wnt2β、Gsk3β、PCNA、CyclinD1 和β-连环蛋白的基因表达,以及 Wnt2β、PCNA 和β-连环蛋白的蛋白表达。另一方面,在 DOP 治疗后鉴定出了 9 种内源性代谢物。其中,甜菜碱是最重要的一种,因为它具有很强的抗氧化活性,从而具有抗肿瘤作用。DOP 可以通过调节 Wnt/β-连环蛋白通路和改变内源性代谢物来抑制 MNNG 诱导的 PLGC 模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3c0/6680496/85e80424aa92/molecules-24-02660-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3c0/6680496/85e80424aa92/molecules-24-02660-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3c0/6680496/7b0e127c3523/molecules-24-02660-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3c0/6680496/535cbc792581/molecules-24-02660-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3c0/6680496/383dd47ef7fb/molecules-24-02660-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3c0/6680496/dd1bfd98bec2/molecules-24-02660-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3c0/6680496/adc3f3c02ece/molecules-24-02660-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3c0/6680496/85e80424aa92/molecules-24-02660-g008.jpg

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