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樟芝中的 4-乙酰基安石榴素 B 增强树突状细胞对肝癌干细胞的免疫功能。

4-Acetylantroquinonol B from antrodia cinnamomea enhances immune function of dendritic cells against liver cancer stem cells.

机构信息

Institute of Food Science and Technology, National Taiwan University, Taipei, 10617, Taiwan.

Institute of Food Science and Technology, National Taiwan University, Taipei, 10617, Taiwan.

出版信息

Biomed Pharmacother. 2019 Jan;109:2262-2269. doi: 10.1016/j.biopha.2018.11.101. Epub 2018 Nov 28.

Abstract

The functions of 4-acetylantroquinonol B (4-AAQB), a ubiquinone derivative isolated from the mycelium of Antrodia cinnamomea, in immunotherapy for liver cancer were investigated. We found that 4-AAQB could inhibit liver cancer stem cell related manifestations and activate the antitumor ability of dendritic cells. Specifically, 4-AAQB can inhibit EpCAM, AFP and related pathways of HepG2 cells. It also significantly decreases the expression of β-catenin, inhibits the tumorigenicity and decreases the secretion of immune escape related cytokines. Moreover, 4-AAQB can stimulate the proliferation of immune cells and promote the endocytosis of immature dendritic cells. When co-cultured immature dendritic cells with EpCAM+ HepG2 cells, 4-AAQB enhanced the expression of MHC class I and II on the surface of liver cancer stem cells and dendritic cells, increased the expression of costimulatory molecules CD80 of dendritic cells and cytokines related to immune activation. In conclusion, 4-AAQB from Antrodia cinnamomea can enhance immune function of dendritic cells against liver cancer stem cells, and may have the potential to be used for liver cancer prevention and immunotherapy.

摘要

我们研究了从红芝菌丝体中分离得到的泛醌衍生物 4-乙酰基安石榴苷 B(4-AAQB)在肝癌免疫治疗中的作用。我们发现 4-AAQB 可以抑制肝癌干细胞相关表现并激活树突状细胞的抗肿瘤能力。具体而言,4-AAQB 可以抑制 EpCAM、AFP 及其在 HepG2 细胞中的相关途径。它还显著降低 β-连环蛋白的表达,抑制致瘤性并降低免疫逃逸相关细胞因子的分泌。此外,4-AAQB 可以刺激免疫细胞的增殖并促进未成熟树突状细胞的内吞作用。当将未成熟的树突状细胞与 EpCAM+ HepG2 细胞共培养时,4-AAQB 增强了肝癌干细胞和树突状细胞表面 MHC Ⅰ类和Ⅱ类分子的表达,增加了树突状细胞共刺激分子 CD80 的表达以及与免疫激活相关的细胞因子。总之,来自红芝的 4-AAQB 可以增强树突状细胞针对肝癌干细胞的免疫功能,并且可能具有用于肝癌预防和免疫治疗的潜力。

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