title: Shenling Baizhu San supresses colitis associated colorectal cancer through inhibition of epithelial-mesenchymal transition and myeloid-derived suppressor infiltration.
abstract: BACKGROUND
  Shenling Baizhu San (SBS) is a well-known and classical Chinese medicine formula. It has been used for treatment of gastrointestinal disorders for about nine hundred years. Recent reports showed that it was effective in curing colitis and ameliorating the major manifestations of postoperational colorectal cancer (CRC). This study was to evaluate the effects of SBS on azoxymethane (AOM) and dextran sodium sulfate (DSS) induced colitis associated CRC (caCRC) and to analyze the underlying mechanism of SBS in preventing CRC.
  
  
  METHODS
  The colon tissue of mice in different group was determined by immunohistochemistry and western blot. TGF-β1 in serum was measured by ELISA. Myeloid-derived suppressor cells (MDSCs) were identified by flow cytometry and immunohistochemistry.
  
  
  RESULTS
  The formed neoplasms phenotypically resembled human caCRC with upregulated β-catenin, p53 and proliferating cell nuclear antigen (PCNA). SBS treatment reduced the death rate of mice and decreased the incidence and multiplicity of colonic neoplasms. SBS decreased the number of MDSCs and the level of transforming growth factor β1 (TGF-β1). SBS alleviated epithelial mesenchymal transition (EMT) through downregulating N-cadherin (N-cad), Vimentin, Fibronectin, Snail, and upregulating E-cadherin (E-cad). It reduced the activation of Wnt5a and EMT induced by TGF-β1.
  
  
  CONCLUSIONS
  SBS reduced the death rate through decreasing the incidence and multiplicity of colonic tumors. SBS lowered MDSCs infiltration and inhibited TGF-β1 induced EMT to exert its anti-caCRC effects.
authors.affiliation: Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. 851917277@qq.com.|The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China. 851917277@qq.com.
authors.forename: Xiaochang
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. 492338026@qq.com.|The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China. 492338026@qq.com.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Xu
authors.affiliation: The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China. 285986672@qq.com.
authors.forename: Meng
authors.initials: M
authors.lastname: Shao
authors.affiliation: The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China. 123744554@qq.com.
authors.forename: Qin
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Department of Imaging Center, Nanfang hospital, Southern Medical University, Guangzhou, 510515, China. wenge67@aliyun.com.
authors.forename: Ge
authors.initials: G
authors.lastname: Wen
authors.affiliation: Department of Anesthesiology, Yue Bei People's Hospital, Shaoguan, Guangdong Province, China. anesthesia@126.com.
authors.forename: Changke
authors.initials: C
authors.lastname: Li
authors.affiliation: Traditional Chinese Medicine Integrated Hospital, Southern Medical University, Guangzhou, 510315, Guangdong, China. jll47379@163.com.
authors.forename: Linlin
authors.initials: L
authors.lastname: Jing
authors.affiliation: Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. sxg_smu@126.com.|The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China. sxg_smu@126.com.
authors.forename: Xuegang
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D001397:Azoxymethane; D015820:Cadherins / Q000378:metabolism; D003092:Colitis / Q000150:complications*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D016264:Dextran Sulfate; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000378:metabolism*; D008517:Phytotherapy; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000097:blood; D014746:Vimentin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D004365:Drugs, Chinese Herbal; D005353:Fibronectins; D018809:Proliferating Cell Nuclear Antigen; D053773:Transforming Growth Factor beta1; D014746:Vimentin; D051176:beta Catenin; D016264:Dextran Sulfate; D001397:Azoxymethane