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酿酒酵母来源的(1→3)-β-D-葡聚糖对S180荷瘤小鼠的抗肿瘤作用

Anti-tumor effects of (1→3)-β-d-glucan from Saccharomyces cerevisiae in S180 tumor-bearing mice.

作者信息

Mo Li, Chen Yafei, Li Wenjian, Guo Shuai, Wang Xuzhao, An Hailong, Zhan Yong

机构信息

Key Laboratory of Molecular Biophysics, Hebei Province, Institute of Biophysics, School of Sciences, Hebei University of Technology, Tianjin 300401, China.

Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.

出版信息

Int J Biol Macromol. 2017 Feb;95:385-392. doi: 10.1016/j.ijbiomac.2016.10.106. Epub 2016 Nov 9.

Abstract

(1→3)-β-d-Glucan from Saccharomyces cerevisiae is a typical polysaccharide with various biological effects and is considered a candidate for the prevention and treatment of cancer in vitro. Research into the function of (1→3)-β-d-glucan in tumor-bearing animals in vivo, however, is limited. Here, we investigated the effects of (1→3)-β-d-glucan from S. cerevisiae on S180 tumor-bearing mice and on the immunity of the tumor-bearing host. The molecular mechanisms underlying the observed effects were investigated. (1→3)-β-d-Glucan was shown to exert anti-tumor effects without toxicity in normal mouse cells. The volume and weight of S180 tumors decreased dramatically following treatment with (1→3)-β-d-glucan, and treatment with the polysaccharide was furthermore shown to increase the tumor inhibition rate in a dose-dependent manner. Spleen index, T lymphocyte subsets (CD and CD), as well as interleukins (IL)-2, (IL-2, IL-6), and tumor necrosis factor-α were assayed to detect the immunoregulatory and anti-tumor effects after (1→3)-β-d-glucan intragastrical administration. (1→3)-β-d-Glucan was shown to significantly potentiate the mouse immune responses by, among other effects, decreasing the ratio of CD to CD. The expression levels of IL-2, IL-6, and TNF-α were also significantly increased by (1→3)-β-d-glucan. These results suggest that (1→3)-β-d-glucan enhances the host's immune function during the tumor inhibition process. S180 tumor cells treated with (1→3)-β-d-glucan also exhibited significant apoptotic characteristics. (1→3)-β-d-glucan increased the ratio of Bax to Bcl-2 at the translation level by up-regulating Bax expression and down-regulating Bcl-2 expression, resulting in the initiation of cell apoptosis in S180 tumor-bearing mice. Taken together, these results indicate that the anti-tumor effects exerted by (1→3)-β-d-glucan may be attributed to the polysaccharide's immunostimulating properties and apoptosis-inducing features. Further investigation into these properties and their associated mechanisms will contribute to the development of potent polysaccharide-based anti-tumor agents.

摘要

来自酿酒酵母的(1→3)-β-d-葡聚糖是一种具有多种生物学效应的典型多糖,在体外被认为是预防和治疗癌症的候选物质。然而,关于(1→3)-β-d-葡聚糖在荷瘤动物体内功能的研究却很有限。在此,我们研究了来自酿酒酵母的(1→3)-β-d-葡聚糖对S180荷瘤小鼠及荷瘤宿主免疫的影响。对所观察到的效应背后的分子机制进行了研究。结果表明,(1→3)-β-d-葡聚糖在正常小鼠细胞中具有抗肿瘤作用且无毒性。用(1→3)-β-d-葡聚糖处理后,S180肿瘤的体积和重量显著减小,并且还显示该多糖处理以剂量依赖方式提高了肿瘤抑制率。检测脾指数、T淋巴细胞亚群(CD和CD)以及白细胞介素(IL)-2、(IL-2、IL-6)和肿瘤坏死因子-α,以检测(1→3)-β-d-葡聚糖灌胃给药后的免疫调节和抗肿瘤作用。结果表明,(1→3)-β-d-葡聚糖通过降低CD与CD的比值等作用显著增强小鼠免疫反应。(1→3)-β-d-葡聚糖还显著提高了IL-2、IL-6和TNF-α的表达水平。这些结果表明,(1→3)-β-d-葡聚糖在肿瘤抑制过程中增强了宿主的免疫功能。用(1→3)-β-d-葡聚糖处理的S180肿瘤细胞也表现出明显的凋亡特征。(1→3)-β-d-葡聚糖通过上调Bax表达和下调Bcl-2表达,在翻译水平上增加了Bax与Bcl-2的比值,从而导致S180荷瘤小鼠细胞凋亡的启动。综上所述,这些结果表明(1→3)-β-d-葡聚糖发挥的抗肿瘤作用可能归因于该多糖的免疫刺激特性和诱导凋亡的特征。对这些特性及其相关机制的进一步研究将有助于开发有效的基于多糖的抗肿瘤药物。

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