Lentinan inhibits tumor angiogenesis via interferon γ and in a T cell independent manner.
Lentinan inhibits tumor angiogenesis via interferon γ and in a T cell independent manner.
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香菇多糖通过干扰素 γ 以 T 细胞独立的方式抑制肿瘤血管生成
DOI：
10.1186/s13046-018-0932-y
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发表时间：
2018-10-29
期刊：
影响因子：
--
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Deng S;Zhang G;Kuai J;Fan P;Wang X;Zhou P;Yang D;Zheng X;Liu X;Wu Q;Huang Y
抗血管生成药物通常用于肺癌和结肠癌的治疗，然而，快速发展的耐药性限制了它们的疗效。香菇多糖（LNT）是从香菇中提取的一种生物活性化合物。采用免疫组化方法观察LNT对小鼠LAP0297肺肿瘤和CT26结肠肿瘤血管生成的影响。采用流式细胞术、qPCR和ELISA检测LNT对肿瘤组织免疫细胞和基因表达的影响。采用裸鼠和IFNγ阻断法研究LNT对肿瘤血管生成的影响机制。使用双尾学生t检验或方差分析对数据集进行比较。我们发现LNT抑制肿瘤血管生成和肺癌和结肠癌的生长。LNT治疗提高了IFNγ等血管抑制因子的表达，也增加了表达IFNγ的T细胞和骨髓细胞的肿瘤浸润。有趣的是，IFNγ阻断，而不是T细胞缺乏，逆转了LNT治疗对肿瘤血管的影响。此外，长期给予LNT持续抑制肿瘤血管生成和抑制肿瘤生长。LNT通过增加IFNγ的产生并以不依赖于T细胞的方式抑制肿瘤血管生成。我们的研究结果表明，LNT可以作为一种新的抗血管生成药物，用于肺癌和结肠癌的长期治疗。本文的在线版本（10.1186/s13046-018-0932-y）包含补充内容，授权用户可使用。
Antiangiogenic agents are commonly used in lung and colon cancer treatments, however, rapid development of drug resistance limits their efficacy. Lentinan (LNT) is a biologically active compound extracted from Lentinus edodes. The effects of LNT on tumor angiogenesis were evaluated by immunohistochemistry in murine LAP0297 lung and CT26 colorectal tumor models. The impacts of LNT on immune cells and gene expression in tumor tissues were determined by flow cytometry, qPCR, and ELISA. Nude mice and IFNγ blockade were used to investigate the mechanism of LNT affecting on tumor angiogenesis. The data sets were compared using two-tailed student’s t tests or ANOVA. We found that LNT inhibited tumor angiogenesis and the growth of lung and colon cancers. LNT treatments elevated the expression of angiostatic factors such as IFNγ and also increased tumor infiltration of IFNγ-expressing T cells and myeloid cells. Interestingly, IFNγ blockade, but not T cell deficiency, reversed the effects of LNT treatments on tumor blood vessels. Moreover, long-lasting LNT administration persistently suppressed tumor angiogenesis and inhibited tumor growth. LNT inhibits tumor angiogenesis by increasing IFNγ production and in a T cell-independent manner. Our findings suggest that LNT could be developed as a new antiangiogenic agent for long-term treatment of lung and colon cancers. The online version of this article (10.1186/s13046-018-0932-y) contains supplementary material, which is available to authorized users.
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DOI：
10.1038/nri.2017.145
发表时间：
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期刊：
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