title: Ganoderma lucidum polysaccharide extract inhibits hepatocellular carcinoma growth by downregulating regulatory T cells accumulation and function by inducing microRNA-125b.
abstract: BACKGROUND
  Ganoderma lucidum polysaccharides (GLPS) have been used as traditional Chinese medicine for their properties of cancer prevention and immunomodulation. However, it is unclear whether GLPS has therapeutic effect on anti-hepatocellular carcinoma (HCC) in vivo. In this study, the effect of GLPS and their impact on the balance of regulatory T cell (Treg) and effector T cell (Teff) was measured in a model of hepatoma-bearing mice.
  
  
  METHODS
  The effect of GLPS and their impact on the balance of regulatory T cell (Treg) and effector T cell (Teff) were measured in a model of hepatoma-bearing mice. Real-time PCR detected the levels of MicroRNAs (miRNAs) and mRNA. The effects of Tregs on Teff proliferation were determined via suppression assay. The mircroRNA-125b (miR-125b) inhibitor was used to down-regulate miR-125b expression.
  
  
  RESULTS
  GLPS significantly suppressed tumor growth in hepatoma-bearing mice associated with an increase of the ratio of Teffs to Tregs. Moreover, GLPS eliminate Treg suppression of Teff proliferation with an increase in IL-2 secretion. Addition of GLPS to treat T cells inhibited Notch1 and FoxP3 expression through increase of miR-125b expression. In hepatoma-bearing mice, miR-125b inhibitor obviously abolished the effect of GLPS on tumor growth.
  
  
  CONCLUSIONS
  This finding provides the novel evidence for GLPS on inhibition of HCC through miR-125b inhibiting Tregs accumulation and function.
authors.affiliation: Department of Pathology, Nanjing Medical University, Nanjing, China. liaimei@163.com.|Department of Nuclear Medicine, The Affiliated Drum Tower Hospital of NanJing University, Zhongshan Road, Nanjing, 210008, China. liaimei@163.com.
authors.forename: Aimei
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Pathology, Nanjing Medical University, Nanjing, China. shuaixuanyu@163.com.
authors.forename: Xuanyu
authors.initials: X
authors.lastname: Shuai
authors.affiliation: Department of Nuclear Medicine, The Affiliated Drum Tower Hospital of NanJing University, Zhongshan Road, Nanjing, 210008, China. jiazhijun@163.com.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of General Surgery, Shengjing Hospital Affiliated to China Medical University, Shenyang, China. lihangyu@163.com.
authors.forename: Hangyu
authors.initials: H
authors.lastname: Li
authors.affiliation: Center of Metabolic Disease Research, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, China. liangxiubin@njmu.edu.cn.
authors.forename: Xiubin
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Pathology, Nanjing Medical University, Nanjing, China. sudongming@njmu.edu.cn.|Center of Cellular Therapy, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. sudongming@njmu.edu.cn.|Center of Metabolic Disease Research, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, China. sudongming@njmu.edu.cn.
authors.forename: Dongming
authors.initials: D
authors.lastname: Su
authors.affiliation: Department of Nuclear Medicine, The Affiliated Drum Tower Hospital of NanJing University, Zhongshan Road, Nanjing, 210008, China. wanhuaguo@163.com.
authors.forename: Wanhua
authors.initials: W
authors.lastname: Guo
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D019169:Jurkat Cells; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011134:Polysaccharides / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*
chemical_list: D035683:MicroRNAs; C527468:Mirn125 microRNA, mouse; D011134:Polysaccharides