机构:[1]Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China[2]The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine[3]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China[4]School of Chinese Medicine integrated with Western Medicine, Binzhou Medical University, Yantai 264003, China[5]Department of Gastrointestinal surgery, Guangdong General Hospital, Guangzhou 510120, China广东省人民医院
To test the hypothesis that modified Shenlingbaizhu decoction (MSD) attenuates the formation of intestinal adenomas by regulating activation of CD4+CD25+ forkhead box P3 (FoxP3) regulatory T cells (Tregs) by downregulation of hypoxia-inducible factor 1α (HIF-1α).
Chemical fingerprints of ginsenoside Rb1, ginsenoside Rc, paeoniflorin, and dioscin in standard extractions were used as material bases of MSD. Adenomatous polyposis coli multiple intestinal neoplasia (ApcMin/+) mice, which harbor a mutation in adenomatous polyposis coli, were used to host intestinal adenomas. Peripheral blood and spleen Tregs were analyzed by flow cytometry. Protein expression was analyzed by immunohistochemistry and Western blotting.
The number and size of intestinal adenomas were significantly reduced by MSD treatment. Mucosal thickening and the spleen size were also substantially decreased by MSD. The carcinogenesis process in ApcMin/+ mice resembled that of human colorectal cancer. Molecular markers of neoplasms, such as β-catenin, cyclooxygenase-2, proliferating cell nuclear antigen, and p53, were substantially ameliorated by MSD treatment. Moreover, MSD downregulated peripheral and spleen CD4+CD25+FoxP3+ Tregs and reduced in situ expression of CD4, CD25, and FoxP3 in intestinal adenomas. MSD also suppressed HIF-1α expression in the intestinal adenomas, and HIF-1α inhibition decreased expression of FoxP3 in Jurkat T cells under hypoxic conditions.
MSD is a valid prescription to control the formation of intestinal adenomas in ApcMin/+ mice. It exerts anti-cancer effects partially through suppression of HIF-1α that induced activation of CD4+CD25+FoxP3+ Tregs in vivo and in vitro.
基金:
The National Science Foundation of China
(No. 81573848; Colorectal Cancer Induces Skeletal Muscle
Autophagy and Glycolysis to Cause Spleen-deficiency;
81774172; TAMs Promote Extreme Deficient Macroenvironment
to Induce Deeply Rooted Colorectal Cancer Stem
Cells), Guangdong Provincial Natural Science Foundation
(No. 2014A030313323; Mechanism Study on Muscle Dystrophy
with Spleen-Deficiency Resulting from Colorectal Cancer
Induced Skeletal Muscle Autophagy), and Specialized Research
Fund for the Doctoral Program of Higher Education
(No. 20134433110007; Mechanism of Parthenolide Regulates
the Opening of Mitochondrial Membrane Permeability
Transition Pore to Induce Cox +/+ Colorectal Cancer
Necroptosis)
语种:
外文
PubmedID:
第一作者:
第一作者机构:[1]Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China[2]The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine[3]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China[4]School of Chinese Medicine integrated with Western Medicine, Binzhou Medical University, Yantai 264003, China
通讯作者:
通讯机构:[1]Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China[2]The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine[3]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China[*1]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
推荐引用方式(GB/T 7714):
Xu Wenjuan,Han Qinrui,Liang Shuntian,et al.Modified Shenlingbaizhu decoction reduces intestinal adenoma formation in adenomatous polyposis coli multiple intestinal neoplasia mice by suppression of hypoxia-inducible factor 1α-induced CD4+CD25+forkhead box P3 regulatory T cells.[J].Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan.2018,38(1):22-32.
APA:
Xu Wenjuan,Han Qinrui,Liang Shuntian,Li Lu,Sun Xuegang...&Xu Wenjuan.(2018).Modified Shenlingbaizhu decoction reduces intestinal adenoma formation in adenomatous polyposis coli multiple intestinal neoplasia mice by suppression of hypoxia-inducible factor 1α-induced CD4+CD25+forkhead box P3 regulatory T cells..Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan,38,(1)
MLA:
Xu Wenjuan,et al."Modified Shenlingbaizhu decoction reduces intestinal adenoma formation in adenomatous polyposis coli multiple intestinal neoplasia mice by suppression of hypoxia-inducible factor 1α-induced CD4+CD25+forkhead box P3 regulatory T cells.".Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan 38..1(2018):22-32