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基于组织工程肿瘤模型检测和评估黄芪多糖的抗癌效率。

Detection and Evaluation of Anti-Cancer Efficiency of Astragalus Polysaccharide Via a Tissue Engineered Tumor Model.

机构信息

State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian, 116024, China.

Burns Research Group, ANZAC Research Institute, Concord Hospital, University of Sydney, Concord, NSW, 2139, Australia.

出版信息

Macromol Biosci. 2018 Nov;18(11):e1800223. doi: 10.1002/mabi.201800223. Epub 2018 Sep 6.

DOI:10.1002/mabi.201800223
PMID:30188006
Abstract

Polysaccharides have been known to display their anti-cancer activity via immunomodulation. The immunomodulation of RAW 246.7 macrophages by astragalus polysaccharide (APS) is herein studied in human breast cancer cells. Apart from traditional 2D culture, a novel tissue-engineered tumor model is prepared based on decellularized porcine lung scaffold. Decellularized lung scaffolds exhibit preferable biocompatibility that promote the formation and enlargement of tumor spheroids. The conditioned medium (CM, the supernatant liquid of APS-treated RAW264.7 macrophages) shows anti-cancer activity by inhibiting cell proliferation, demonstrated by a 39.25 ± 5.04% decrease in tumoroid size and 20.96 ± 2.43% reduction in cell viability, and promoting cell apoptosis by the nuclear fragmentation and increasing apoptotic-stage proportion. The cytotoxicity of CM is associated with the upregulated production of nitric oxide and tumor necrosis factor-α from RAW 246.7 cells stimulated by APS. Overall, by using this 3D tumor model to study CM, there is convincing evidence that APS can modulate macrophage function to further mediate anti-cancer activity.

摘要

多糖已被证实通过免疫调节发挥其抗癌活性。本研究旨在探讨黄芪多糖(APS)对 RAW 246.7 巨噬细胞的免疫调节作用及其在人乳腺癌细胞中的作用。除了传统的二维培养外,我们还基于脱细胞猪肺支架制备了一种新型组织工程肿瘤模型。脱细胞肺支架表现出较好的生物相容性,促进了肿瘤球体的形成和增大。条件培养基(CM,APS 处理的 RAW264.7 巨噬细胞的上清液)通过抑制肿瘤球体的大小(减少 39.25±5.04%)和细胞活力(降低 20.96±2.43%)来显示抗癌活性,并通过核碎裂和增加凋亡阶段比例促进细胞凋亡。CM 的细胞毒性与 APS 刺激 RAW 246.7 细胞产生的一氧化氮和肿瘤坏死因子-α的上调有关。总的来说,通过使用这种 3D 肿瘤模型来研究 CM,有充分的证据表明 APS 可以调节巨噬细胞功能,进一步介导抗癌活性。

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