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对台湾金线莲中结构特征明确的阿拉伯半乳聚糖作为BALB/c小鼠CT26结肠癌免疫调节剂的研究。

Structurally characterized arabinogalactan from Anoectochilus formosanus as an immuno-modulator against CT26 colon cancer in BALB/c mice.

作者信息

Yang Li-Chan, Hsieh Chang-Chi, Lu Ting-Jang, Lin Wen-Chuan

机构信息

Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan.

Department of Animal Science and Biotechnology, Tunghai University, Taichung, Taiwan.

出版信息

Phytomedicine. 2014 Apr 15;21(5):647-55. doi: 10.1016/j.phymed.2013.10.032. Epub 2013 Dec 4.

Abstract

In this study, the innate immuno-modulatory effects and anti-cancer action of arabinogalactan (AG), a derivative of a well-known orchid, Anoectochilus formosanus, were investigated. The innate immuno-modulatory effects of AG were determined in vitro using RAW 264.7 cells for microarray analysis, and in vivo using BALB/c mice administrated with AG at 5 and 15 mg/kg intra-peritoneally for 3 weeks. The anti-cancer activity of AG was evaluated by CT26 colon cancer-bearing BALB/c mice. The microarray analysis was performed to evaluate the innate immunity and demonstrated that AG significantly induced the expression of cytokines, chemokines, and co-stimulatory receptors, such as IL-1α, CXCL2, and CD69. An intraperitoneal injection of AG in mice increased the spleen weight, but not the body weight. The treatment of mitogen, LPS significantly stimulated splenocyte proliferation in AG treated groups. The AG treatment also promoted splenocyte cytotoxicity against YAC-1 cells and increased the percentage of CD3(+)CD8(+) cytotoxic T cells in innate immunity test. Our experiments revealed that AG significantly decreased both tumour size and tumour weight. Besides, AG increased the percentage of DC, CD3(+)CD8(+) T cells, CD49b(+)CD3(-) NK cells among splenocytes, and cytotoxicity activity in tumour-bearing mice. In addition, the immunohistochemistry of the tumour demonstrated that the AG treatments increased the tumour-filtrating NK and cytotoxic T-cell. These results demonstrated that AG, a polysaccharide derived from a plant source, has potent innate immuno-modulatory and anti-cancer activity. AG may therefore be used for cancer immunotherapy.

摘要

在本研究中,对一种著名兰花金线莲的衍生物阿拉伯半乳聚糖(AG)的先天免疫调节作用和抗癌作用进行了研究。使用RAW 264.7细胞在体外进行微阵列分析以确定AG的先天免疫调节作用,并在体内使用腹腔注射5和15 mg/kg AG的BALB/c小鼠,持续3周。通过携带CT26结肠癌的BALB/c小鼠评估AG的抗癌活性。进行微阵列分析以评估先天免疫,结果表明AG显著诱导细胞因子、趋化因子和共刺激受体如IL-1α、CXCL2和CD69的表达。给小鼠腹腔注射AG增加了脾脏重量,但未增加体重。在AG处理组中,丝裂原LPS的处理显著刺激了脾细胞增殖。AG处理还促进了脾细胞对YAC-1细胞的细胞毒性,并在先天免疫试验中增加了CD3(+)CD8(+)细胞毒性T细胞的百分比。我们的实验表明,AG显著降低了肿瘤大小和肿瘤重量。此外,AG增加了荷瘤小鼠脾细胞中DC、CD3(+)CD8(+) T细胞、CD49b(+)CD3(-) NK细胞的百分比以及细胞毒性活性。此外,肿瘤的免疫组织化学显示,AG处理增加了肿瘤浸润性NK细胞和细胞毒性T细胞。这些结果表明,AG这种源自植物的多糖具有强大的先天免疫调节和抗癌活性。因此,AG可用于癌症免疫治疗。

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