偶氮甲烷
癌变
癌症研究
肿瘤微环境
免疫抑制
结直肠癌
免疫系统
体内
医学
车站3
缺氧(环境)
免疫学
癌症
药理学
生物
化学
内科学
信号转导
细胞生物学
有机化学
氧气
生物技术
作者
Yuli Zhang,Ni Chai,Zhenzhen Wei,Zan Li,Lu Zhang,Jun Zhang,J. Ren,Renjie Xu,Xiufeng Pang,Bi-Meng Zhang,Qingfeng Tang,Hua Sui
出处
期刊:Phytomedicine
[Elsevier]
日期:2022-01-02
卷期号:98: 153917-153917
被引量:23
标识
DOI:10.1016/j.phymed.2021.153917
摘要
The occurrence of colorectal cancer (CRC) is associated with a variety of factors. Accumulating evidence shows that peripheral differentiation of regulatory T cells (Tregs) is critical in controlling tumorigenesis. Our previous studies demonstrated that the Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS) extract exerted potent anticancer activities by significantly enhancing immunosuppression in ApcMin/+ mice. However, there is limited knowledge on the effect of YYFZBJS in the prevention of colorectal cancer and the underlying mechanisms of action.In this study, we investigated the effect of oral administration of YYFZBJS in preventing azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced tumorigenesis. We found that YYFZBJS treatment decreased tumor load, tumor number, histology, and the severity of disease activity index (DAI) scores. To investigate if YYFZBJS inhibited tumorigenesis by regulating regulatory T cells, we depleted Tregs in AOM/DSS mice. We then analyzed the effect of intragastric administration of YYFZBJS on tumorigenesis and the regulation of tumor microenvironment.As expected, intragastric administration of YYFZBJS in AOM/DSS mice model significantly increased immune responses in the tumor microenvironment through its hypoxia-associated anti-cancer activities. Additionally, YYFZBJS regulated the polarization of peripheral Treg (pTreg) to suppress CRC cell proliferation and infiltration. This was demonstrated by the decrease in tumor proliferation-related proteins including p-STAT3, p-NF-κB and MMPs in a dose-dependent manner. Clinically, the increase in the levels of Tregs in human tissues during CRC progression was associated with low expression of HIF-1α in the stroma, and correlated with CRC survival and prognosis.Altogether, we demonstrated that HIF-1α may promote pTreg -induced carcinogenesis and progression of CRC cells, indicating that YYFZBJS is a promising protective agent against HIF-1α-mediated Treg activation in colorectal cancer. This study is the first to imply a novel clinical significance of a traditional Chinese herbal medicine from Synopsis of Golden Chamber in the cancer treatment and clarify the important role of tumor microenvironment in preventing tumorigenesis.
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