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Journal of Traditional Chinese Medicine ›› 2018, Vol. 38 ›› Issue (01): 22-32.

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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

Xu Wenjuan, Han Qinrui, Liang Shuntian, Li Lu, Shao Meng, Yao Xueqing, Sun Xuegang   

  1. Department of Traditional Chinese Medicine,Nanfang Hospital, Southern Medical University;The Key Laboratory of Molecular Biology,State Administration of Traditional Chinese Medicine;School of Traditional Chinese Medicine, Southern Medical University;School of Chinese Medicine integrated with Western Medicine, Binzhou Medical University;Department of Traditional Chinese Medicine, Nanfang Hospital,Southern Medical University;The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine; School of Traditional Chinese Medicine, Southern Medical University;Department of Gastrointestinal surgery,Guangdong General Hospital;
  • Online:2018-02-15 Published:2018-02-15
  • Supported by:
    Supported by 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), 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)

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Abstract: OBJECTIVE: To test the hypothesis that modified Shenlingbaizhu decoction(MSD) attenuates the formation of intestinal adenomas by regulating activation of CD4+CD25+ forkhead box P3(Fox P3) regulatory T cells(Tregs) by downregulation of hypoxia-inducible factor 1α(HIF-1α).METHODS: 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.RESULTS: 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 substan-tially ameliorated by MSD treatment. Moreover,MSD downregulated peripheral and spleen CD4 +CD25+Fox P3+ Tregs and reduced in situ expression of CD4, CD25, and Fox P3 in intestinal adenomas.MSD also suppressed HIF-1α expression in the intestinal adenomas, and HIF-1α inhibition decreased expression of Fox P3 in Jurkat T cells under hypoxic conditions.CONCLUSION: 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+Fox P3+ Tregs in vivo and in vitro.

Key words: Colorectal neoplasms, T-lymphocytes, regulatory, Hypoxia-inducible factor 1, alpha subunit, Forkhead transcription factors, Modified Shenlingbaizhu decoction

Cite this article

Xu Wenjuan, Han Qinrui, Liang Shuntian, Li Lu, Shao Meng, Yao Xueqing, Sun Xuegang. 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, 2018, 38(01): 22-32.