title: Inhibitory Effect of Anti-rheumatic Drug Iguratimod for Hepatocellular Carcinogenesis by Inhibition of Serum Interleukin-8 Production.
abstract: OBJECTIVE
  Angiogenesis is a known factor for the development of hepatocellular carcinoma (HCC). The aim of this study was to assess the property of iguratimod, that is an anti-inflammatory drug for rheumatoid arthritis, on anti-angiogenesis and anti-carcinogensis for HCC.
  
  
  METHODS
  In vitro, human umbilical vein endothelial cells were cultured under interleukin-8 (IL-8) with or without iguratimod. In vivo, a rat model with HCC received iguratimod or distilled water for 6 weeks. Diameter of the largest tumor, number of tumors and serum interleukin-8 concentration were compared between iguratimod and control groups.
  
  
  RESULTS
  By an in vitro angiogenesis assay, it was found angiogenesis in iguratimod group was significantly lower than that in control group (p=0.013). In vivo, largest tumor diameter (p=0.036), number of the tumor (p=0.011) and serum interleukin-8 concentration (p=0.036) in the iguratimod group were significantly smaller and lower than those in the control group.
  
  
  CONCLUSIONS
  Iguratimod may inhibit hepatocellular carcinogensis by inhibition of interleukin-8 production in a rat model.
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan sakamo@jikei.ac.jp.
authors.forename: Taro
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishii
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shiba
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Kenei
authors.initials: K
authors.lastname: Furukawa
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Haruki
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Iwase
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Shirai
authors.affiliation: Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yanaga
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology*; D018920:Coculture Techniques; D005347:Fibroblasts; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000097:blood; D008114:Liver Neoplasms, Experimental / Q000097:blood / Q000098:blood supply / Q000188:drug therapy*; D008297:Male; D009389:Neovascularization, Pathologic / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D018501:Antirheumatic Agents; D002867:Chromones; D016209:Interleukin-8; D013449:Sulfonamides; C519076:iguratimod
keywords: Hepatocellular carcinoma; iguratimod; interleukin-8; rat