IFN-alpha2b and thalidomide synergistically inhibit tumor-induced angiogenesis

J Interferon Cytokine Res. 2003 Jan;23(1):3-10. doi: 10.1089/10799900360520397.


Angiogenesis is an absolute requirement for tumor growth and metastasis. The purpose of this study was to evaluate the antiangiogenic activity of interferon-alpha2b (IFN-alpha2b) and thalidomide, as single agents and in combination. The murine dermis model was used to assess tumor-induced angiogenesis in nude mice. Human ACHN (renal), NIH-OVCAR-3 (ovarian), LNCaP (prostate), and SK-Mel-1 (melanoma) tumor cells were inoculated intradermally into the flanks of nude mice. IFN-alpha2b and thalidomide, administered daily, were effective inhibitors of angiogenesis induced by all four tumor types. The combination of IFN-alpha2b and thalidomide caused a synergistic decrease in mean vessel count in tumors that were resistant to the antiproliferative effects of IFN-alpha2b and thalidomide in vitro. This enhanced suppression of angiogenesis translated into synergistic antitumor activity in a xenograft model. Pegylated IFN-alpha (PEG-IFN-alpha2b) (10(6) U) administered once in 10 days was as effective as daily IFN-alpha2b treatment (10(6) U x 10 days). IFN-alpha2b and thalidomide have potentiated antiangiogenic activity when used in combination. A single dose of PEG-IFN-alpha2b (10(6) U) was as effective at suppressing vessel growth as an equivalent dose of IFN-alpha2b given daily for 10 days.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage*
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Cell Division / drug effects
  • Drug Administration Schedule
  • Drug Synergism
  • Female
  • Humans
  • Interferon alpha-2
  • Interferon-alpha* / administration & dosage*
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplasms, Experimental / blood supply*
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / pathology
  • Neovascularization, Pathologic / prevention & control*
  • Polyethylene Glycols*
  • Recombinant Proteins
  • Thalidomide / administration & dosage*
  • Transplantation, Heterologous
  • Tumor Cells, Cultured


  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • Thalidomide
  • peginterferon alfa-2b
  • peginterferon alfa-2a