中国中药杂志

2021, v.46(19) 5072-5079

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灵芝多糖通过调节内皮细胞ICAM-1表达促进T淋巴细胞肿瘤浸润的研究
Ganoderma lucidum polysaccharides promote T lymphocyte infiltration into tumor by regulating expression of ICAM-1 in endothelial cells

许晓燕;罗霞;宋怡;周州;李芳;余梦瑶;
XU Xiao-yan;LUO Xia;SONG Yi;ZHOU Zhou;LI Fang;YU Meng-yao;Sichuan Academy of Chinese Medical Sciences;Sichuan Provincial Key Laboratory of Medicinal Materials Quality and Drug Discovery in Traditional Chinese Medicine;Laboratory for Systematic Research and Development of Fungus Medicinal Materials;

摘要(Abstract):

多糖是灵芝发挥肿瘤预防治疗作用的主要有效成分之一,但其是否能在肿瘤免疫疗法中起到协同作用目前尚未明确。该研究通过对灵芝多糖促进T淋巴细胞肿瘤浸润的作用评价和机制研究,以期为其在肿瘤免疫疗法中的应用提供参考。采用水提醇沉法结合Sevag法制备灵芝多糖。分别以25、50、100 mg·kg~(-1)剂量腹腔注射灵芝多糖,评价其对B16-F10荷瘤小鼠肿瘤生长的作用。采用免疫组化法检测肿瘤组织内CD3~+、CD8~+ T细胞浸润情况和细胞间黏附分子-1(ICAM-1)表达水平。以50、100、200μg·mL~(-1)的灵芝多糖处理EA.hy926细胞,采用Western blot法测定ICAM-1表达水平。运用荧光标记的Jurkat细胞,测定灵芝多糖处理的EA.hy926细胞黏附能力。采用Western blot法检测核因子κB(NF-κB)p65、核因子κB抑制因子(IκBα)、p-NF-κB p65、p-IκBα蛋白水平,分析基于NF-κB通路的作用机制。研究结果表明,灵芝多糖能够显著抑制B16-F10荷瘤小鼠肿瘤生长,增加CD3~+、CD8~+ T细胞肿瘤浸润,促进肿瘤组织内ICAM-1表达;灵芝多糖可促进EA.hy926细胞生成ICAM-1,增加其对Jurkat细胞的黏附作用,诱导IκBα的磷酸化与蛋白降解,增强NF-κB p65的表达及其磷酸化水平。以上结果提示,灵芝多糖能够通过NF-κB通路促进ICAM-1表达,并进一步增强T淋巴细胞肿瘤浸润,从而发挥抑制肿瘤生长的作用。该研究结果可为灵芝多糖后续在肿瘤免疫疗法中的应用奠定相关基础。
Polysaccharide is among the main active components of Ganoderma lucidum for tumor prevention and treatment. Howe-ver, it remains unclear whether it has synergy with tumor immunotherapy. This study evaluated the effect of G. lucidum polysaccharides(GLP) on the infiltration of T lymphocytes into tumor and the underlying mechanism, in order to provide a reference for its application in tumor immunotherapy. GLP were prepared by water extraction and alcohol precipitation combined with Sevag method and then given(intraperitoneal injection) to the mice bearing B16-F10 cells at 25, 50 and 100 mg kg~(-1), respectively, to evaluate the effect on tumor growth. The infiltration of CD3~+ and CD8~+ T cells and the expression of intercellular cell adhesion molecule-1(ICAM-1) in tumor were detected by immunohistochemistry. EA.hy926 cells were treated with 50, 100 and 200 μg·mL~(-1) GLP, and the expression of ICAM-1 was determined by Western blot. The adhesion of EA.hy926 cells treated with GLP was measured with fluorescence-labeled Jurkat cells. To analyze the mechanism based on NF-κB pathway, this study determined the protein levels of nuclear factor kappa-B(NF-κB) p65, alpha inhibitor of NF-κB(IκBα), p-NF-κB p65 and p-IκBα by Western blot. The results showed that GLP can significantly inhibit the tumor growth in mice bearing B16-F10 cells, promote the infiltration of CD3~+ and CD8~+ T cells in tumor, and increase the expression of ICAM-1 in tumor. Meanwhile, GLP could also enhance the expression of ICAM-1 in EA.hy926 cells, thus strengthen the adhesion to Jurkat cells, induce phosphorylation and protein degradation of IκBα, and raise the expression and phosphorylation level of NF-κB p65. These results suggested that GLP could promote the expression of ICAM-1 through NF-κB pathway and further enhance the infiltration of T lymphocytes into tumor, thereby inhibiting tumor growth. This study lays a foundation for the further application of GLP in tumor immunotherapy.

关键词(KeyWords): 灵芝多糖;肿瘤;T淋巴细胞;ICAM-1;内皮细胞
Ganoderma lucidum polysaccharides;tumor;T lymphocyte;ICAM-1;endothelial cell

Abstract:

Keywords:

基金项目(Foundation): 四川省省级科研院所基本科研业务费项目(A-2019N-23);; 国家现代农业产业技术体系四川食用菌创新团队项目(SCCXTD-2021-07);; 四川省农业微生物资源共享平台建设项目(2019JDPT0012);; 四川省十四五中药材育种攻关——灵芝新品种选育及配套技术研究项目(2021YFYZ0012)

作者(Author): 许晓燕;罗霞;宋怡;周州;李芳;余梦瑶;
XU Xiao-yan;LUO Xia;SONG Yi;ZHOU Zhou;LI Fang;YU Meng-yao;Sichuan Academy of Chinese Medical Sciences;Sichuan Provincial Key Laboratory of Medicinal Materials Quality and Drug Discovery in Traditional Chinese Medicine;Laboratory for Systematic Research and Development of Fungus Medicinal Materials;

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