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Green Tea Polyphenol EGCG Attenuates MDSCs-mediated Immunosuppression through Canonical and Non-Canonical Pathways in a 4T1 Murine Breast Cancer Model

文献类型： 外文期刊

作者： Xu, Ping 1 ; Yan, Feng 2 ; Zhao, Yueling 1 ; Chen, Xiangbo 3 ; Sun, Shili 4 ; Wang, Yuefei 1 ; Ying, Le 1 ;

作者机构： 1.Zhejiang Univ, Dept Tea Sci, Hangzhou 310058, Peoples R China

2.Monash Univ, Australian Ctr Blood Dis, Cent Clin Sch, Melbourne, Vic 3004, Australia

3.Northeast Normal Univ, Minist Educ, Key Lab Mol Epigenet, Changchun 130024, Peoples R China

4.Guangdong Acad Agr Sci, Tea Res Inst, Guangzhou 510640, Peoples R China

5.Hudson Inst Med Res, Ctr Innate Immun & Infect Dis, Clayton, Vic 3168, Australia

关键词： EGCG; anti-tumor mechanism; MDSCs; immunosuppression; non-canonical pathways

期刊名称：NUTRIENTS （ 影响因子：5.717； 五年影响因子：6.349 ）

ISSN：

年卷期： 2020 年 12 卷 4 期

页码：

收录情况： SCI

摘要： Several studies in the past decades have reported anti-tumor activity of the bioactive compounds extracted from tea leaves, with a focus on the compound epigallocatechin-3-gallate (EGCG). However, further investigations are required to unravel the underlying mechanisms behind the anti-tumor activity of EGCG. In this study, we demonstrate that EGCG significantly inhibits the growth of 4T1 breast cancer cells in vitro and in vivo. EGCG ameliorated immunosuppression by significantly decreasing the accumulation of myeloid-derived suppressor cells (MDSCs) and increasing the proportions of CD4(+) and CD8(+) T cells in spleen and tumor sites in 4T1 breast tumor-bearing mice. Surprisingly, a low dose of EGCG (0.5-5 mu g/mL) effectively reduced the cell viability and increased the apoptosis rate of MDSCs in vitro. EGCG down-regulated the canonical pathways in MDSCs, mainly through the Arg-1/iNOS/Nox2/NF-kappa B/STAT3 signaling pathway. Moreover, transcriptomic analysis suggested that EGCG also affected the non-canonical pathways in MDSCs, such as ECM-receptor interaction and focal adhesion. qRT-PCR further validated that EGCG restored nine key genes in MDSCs, including Cxcl3, Vcan, Col4a1, Col8a1, Oasl2, Mmp12, Met, Itsnl and Acot1. Our results provide new insight into the mechanism of EGCG-associated key pathways/genes in MDSCs in the murine breast tumor model.

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