Inhibitory Effect of Anti-rheumatic Drug Iguratimod for Hepatocellular Carcinogenesis by Inhibition of Serum Interleukin-8 Production

Anticancer Res. 2016 Jul;36(7):3301-6.

Abstract

Background/aim: 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.

Materials and 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.

Conclusion: Iguratimod may inhibit hepatocellular carcinogensis by inhibition of interleukin-8 production in a rat model.

Keywords: Hepatocellular carcinoma; iguratimod; interleukin-8; rat.

MeSH terms

  • Animals
  • Antirheumatic Agents / pharmacology
  • Chromones / pharmacology*
  • Coculture Techniques
  • Fibroblasts
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Interleukin-8 / antagonists & inhibitors*
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / blood
  • Liver Neoplasms, Experimental / blood
  • Liver Neoplasms, Experimental / blood supply
  • Liver Neoplasms, Experimental / drug therapy*
  • Male
  • Neovascularization, Pathologic / blood
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / metabolism
  • Rats
  • Rats, Inbred F344
  • Sulfonamides / pharmacology*

Substances

  • Antirheumatic Agents
  • Chromones
  • Interleukin-8
  • Sulfonamides
  • iguratimod