title: Long-Term Administration of Fibroblast Growth Factor 21 Prevents Chemically-Induced Hepatocarcinogenesis in Mice.
abstract: OBJECTIVE
  In this study, we explored whether treatment with FGF-21 could prevent diethylnitrosamine (DEN) induced hepatocarcinogenesis in mice.
  
  
  RESULTS
  Hepatoma was induced by injection of DEN every three days for 18 weeks. For the prophylactic experiment, mice were firstly injected with FGF-21 for 2 weeks, then FGF-21 was administered to the mice once daily in association with DEN injection till the end of the experiment. The hepatoma incidence of mice treated with FGF-21 was 13.3%, while the incidence of mice treated with saline was 61.5%. To understand the mechanisms, we compared the expression of βklotho (KLB) and oxidative stress level in the livers between the mice treated with FGF-21 and saline. We found that FGF-21 could suppress DEN-induced oxidative stress and up-regulate the expression of KLB in the livers. To confirm these results, we compared the expression of KLB in L02 cells stimulated with or without FGF-21. Besides, we established DEN-induced oxidative stress cell model to affirm the relationship between FGF-21 and DEN-induced oxidative stress in vitro. Results showed that FGF-21 increased the expression of KLB and diminished the DEN-induced oxidative stress in vitro in a dose dependent manner.
  
  
  CONCLUSIONS
  Systemic administration of FGF-21 can prevent DEN-induced hepatocarcinogenesis via suppressing oxidative stress and increasing the expression of KLB.
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, 59 Mucai Street, Harbin, 150030, People's Republic of China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Xu
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, 59 Mucai Street, Harbin, 150030, People's Republic of China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, 59 Mucai Street, Harbin, 150030, People's Republic of China.
authors.forename: Wenfei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, 59 Mucai Street, Harbin, 150030, People's Republic of China.
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, 59 Mucai Street, Harbin, 150030, People's Republic of China.
authors.forename: Zhihang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, 59 Mucai Street, Harbin, 150030, People's Republic of China.|College of Science, University of Baghdad, Baghdad, Iraq.
authors.forename: Lubna Muhi
authors.initials: LM
authors.lastname: Rasoul
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, 59 Mucai Street, Harbin, 150030, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, 59 Mucai Street, Harbin, 150030, People's Republic of China.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, 59 Mucai Street, Harbin, 150030, People's Republic of China.
authors.forename: Xianlong
authors.initials: X
authors.lastname: Ye
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, 59 Mucai Street, Harbin, 150030, People's Republic of China. deshanli@163.com.|Key Laboratory of Agricultural Biological Functional Gene, Northeast Agricultural University, Harbin, People's Republic of China. deshanli@163.com.
authors.forename: Deshan
authors.initials: D
authors.lastname: Li
authors.affiliation: Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, 59 Mucai Street, Harbin, 150030, People's Republic of China. renguiping@126.com.
authors.forename: Guiping
authors.initials: G
authors.lastname: Ren
mesh_terms: D000818:Animals; D015153:Blotting, Western; D063646:Carcinogenesis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004052:Diethylnitrosamine / Q000494:pharmacology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D007150:Immunohistochemistry; D000090265:Klotho Proteins; D008113:Liver Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009374:Neoplasms, Experimental / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects*; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012016:Reference Values; D012680:Sensitivity and Specificity
chemical_list: C418622:Klb protein, mouse; D008565:Membrane Proteins; C414620:fibroblast growth factor 21; D004052:Diethylnitrosamine; D005346:Fibroblast Growth Factors; D000090265:Klotho Proteins
keywords: Diethylnitrosamine; FGF-21; Hepatoma; Oxidative stress; βklotho