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Anti-tumor effect study of Astragalus polysaccharide promotes dendritic cell through TLR4 signal pathway
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DOI   10.11656/j.issn.1673-9043.2022.02.20
Key Words   Astragalus polysaccharides;dendritic cell;TLR4 pathway;anti-tumor
Author NameAffiliationE-mail
JIA Beitian Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
WANG Li Tianjin Second People's Hospital, Tianjin 300192, China  
CUI Huantian Shandong University, Qingdao 266237, China  
JIN Yutong Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
CAO Min Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
LIU Haizhao Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
BIAN Yuhong Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China bianyuhong_2012@163.com 
Abstract
    [Objective] The aim of this study is to investigate the anti-tumor effect of Astragalus polysaccharides (APS) activated dendritic cell (DCs) via the TLR4 signaling pathway. [Methods] The DC2.4 were randomly divided into Control group,APS group,TNF-α group,APS+TNF-α group,TAK-242+TNF-α group,TAK-242+APS+TNF-α group,ST2825+TNF-α group and ST2825+APS+TNF-α group. After 72h of intervention,the ratio of CD80+CD86+ DCs were detected by flow cytometry,and the effect of DCs on the secretion of cytokine IL-12 were detected by ELISA. Then the DCs in previous step were co-cultured with T cells,and effects of DCs on T cell activation were detected by ELISA;the activated CTL cells were co-cultured with tumor cells CT 26,tumor-cell-killing efficiency was calculated using the full-field cell imaging analyzer. [Results] Compared with the control group,APS can significantly promote the expression of CD80+CD86+ DCs and the secretion of IL-12 (P<0.05),and the best effects were obtained when APS and TNF-α were synergistically intervened. In addition,the DCs intervened by APS+TNF-α could significantly promote proliferation of T cells,the secretion of IL-2 by T cells and enhance the killing of tumors by CTL (P<0.05). However,after adding the TLR4 pathway blocker TAK-242 or ST2825,the expression of CD80+CD86+ DCs and the secretion level of IL-12 in APS+TNF-α group were not significantly different from those in the TNF-α group. Compared with the TNF-α group,there was no significant difference in proliferation of T cells,the level of IL-2 secretion and tumor killing by T cells in APS+TNF-α group with blocker TAK-242 or ST2825. [Conclusion] APS could induce DCs maturation and increase the activating ability of DC on T cells. These effects and mechanism may through TLR4/MyD88 pathway,and APS/TNF-a combination treatment to DCs is the best.

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