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YYFZBJS inhibits colorectal tumorigenesis by enhancing Tregs-induced immunosuppression through HIF-1α mediated hypoxia in vivo and in vitro.

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收录情况： ◇ SCIE

作者：
Zhang Yuli[1,2] * ; Chai Ni[2] * ; Wei Zhenzhen[3] * ; Li Zan[1] ; Zhang Lu[4] ; Zhang Mengjie[1] ; Ren Junze[5] ; Xu Renjie[6] ; Pang Xiufeng[7] ; Zhang Bimeng[8] ; Tang Qingfeng[1,9,*1] ; Sui Hua[1] ;
机构： [1]Medical Experiment Center, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201803, China [2]Oncology department, Yueyang Hospital of Integrated of Traditional Chinese and western medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China [3]Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China [4]Department of Integrated Chinese and Western Medicine, Henan Cancer Hospital, Affiliated Hospital of Zhengzhou University, Zhengzhou 450008, China [5]Changhai Hospital of Traditional Chinese Medicine, Naval Medical University, Shanghai 200433, China [6]Department of Rehabilitation Medicine, PLA Marine Corps Hospital, Guangdong 521011, China [7]Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China [8]Department of Acupuncture and Moxibustion, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China [9]Department of Clinical Laboratory, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201803, China
出处：
DOI： 10.1016/j.phymed.2021.153917
ISSN：

关键词： Colorectal cancer HIF-1α AOM/DSS-induced colitis-associated colorectal cancer Tregs Traditional Chinese herb medicine

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.Copyright © 2022 The Author(s). Published by Elsevier GmbH.. All rights reserved.

基金：
National Natural Science Foundation of China (Nos. 81973808, 82174459), the Science Foundation for Shanghai Committee of Science Project (No. 21S21901400, 19411972400, 19ZR1447800), Clinical Research Plan of SHDC (No. SHDC2020CR4047). Shanghai Municipal Health Commission (201840002, 202140198), "Jiaotong University Star" Program (YG2022QN082)
语种：
外文
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PubmedID：
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出版当年[2021]版：
大类 | 2 区 医学
小类 | 1 区 植物科学 1 区 全科医学与补充医学 1 区 药学 2 区 药物化学
最新[2025]版：
大类 | 1 区 医学
小类 | 1 区 药物化学 1 区 全科医学与补充医学 1 区 药学 1 区 植物科学
JCR分区：
出版当年[2020]版：
Q1 PHARMACOLOGY & PHARMACY Q1 PLANT SCIENCES Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Q1 CHEMISTRY, MEDICINAL
最新[2023]版：
Q1 CHEMISTRY, MEDICINAL Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Q1 PHARMACOLOGY & PHARMACY Q1 PLANT SCIENCES

影响因子： 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

第一作者：
第一作者机构： [1]Medical Experiment Center, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201803, China [2]Oncology department, Yueyang Hospital of Integrated of Traditional Chinese and western medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
共同第一作者：
通讯作者：
通讯机构： [1]Medical Experiment Center, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201803, China [9]Department of Clinical Laboratory, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201803, China [*1]Medical Experiment Center, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201803, China
推荐引用方式(GB/T 7714)：
Zhang Yuli,Chai Ni,Wei Zhenzhen,et al.YYFZBJS inhibits colorectal tumorigenesis by enhancing Tregs-induced immunosuppression through HIF-1α mediated hypoxia in vivo and in vitro.[J].PHYTOMEDICINE.2022,98:doi:10.1016/j.phymed.2021.153917.
APA：
Zhang Yuli,Chai Ni,Wei Zhenzhen,Li Zan,Zhang Lu...&Sui Hua.(2022).YYFZBJS inhibits colorectal tumorigenesis by enhancing Tregs-induced immunosuppression through HIF-1α mediated hypoxia in vivo and in vitro..PHYTOMEDICINE,98,
MLA：
Zhang Yuli,et al."YYFZBJS inhibits colorectal tumorigenesis by enhancing Tregs-induced immunosuppression through HIF-1α mediated hypoxia in vivo and in vitro.".PHYTOMEDICINE 98.(2022)

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