Interferon-alphaCon1 suppresses proliferation of liver cancer cell lines in vitro and in vivo

J Hepatol. 2004 Nov;41(5):782-9. doi: 10.1016/j.jhep.2004.07.012.

Abstract

Background/aims: We investigated the effects of consensus interferon (IFN-alphaCon1), a nonnaturally occurring type I interferon with higher specific activity than other type I IFNs, on the growth of human liver cancer cells.

Methods: The effect of IFN-alphaCon1 on the proliferation of 13 liver cancer cell lines was investigated in vitro. Hepatocellular carcinoma (HCC) cells (KIM-1 and HAK-1B) were transplanted subcutaneously into the back of nude mice, then IFN-alphaCon1 was subcutaneously administered to the mice once a day for 2 weeks, and tumor volume and histology were examined.

Results: IFN-alphaCon1 expressed a dose-dependent growth inhibitory effect in all cell lines in vitro. KIM-1 tumor volume in mice that received 0.01 microg (10(4)IU)/mouse/day of IFN-alphaCon1 (similar to the clinical dose for chronic hepatitis C) was 62% of the control, 0.1microg/mouse/day resulted in 26%, and 1 microg/mouse/day resulted in 10%. HAK-1B tumor volume under the same treatment was 61, 24 and 0% of the control, respectively. The number of apoptotic cells significantly increased and the number of blood vessels significantly decreased with the increase in IFN-alphaCon1 dose.

Conclusions: IFN-alphaCon1 suppressed HCC growth in nude mice. These data indicate the potential clinical application of IFN-alphaCon1 in the prevention and treatment of HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antiviral Agents / pharmacology*
  • Apoptosis / drug effects
  • Bile Duct Neoplasms / drug therapy
  • Bile Duct Neoplasms / pathology
  • Bile Ducts, Intrahepatic
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Cholangiocarcinoma / drug therapy
  • Cholangiocarcinoma / pathology
  • Humans
  • In Vitro Techniques
  • Interferon Type I / pharmacology*
  • Interferon-alpha
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Recombinant Proteins

Substances

  • Antineoplastic Agents
  • Antiviral Agents
  • Interferon Type I
  • Interferon-alpha
  • Recombinant Proteins
  • interferon alfacon-1