IFN-alpha2b and thalidomide synergistically inhibit tumor-induced angiogenesis.
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.
Bauer
Joseph A
JA
Taussig Cancer Center, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Morrison
Bei H
BH
Grane
Ronald W
RW
Jacobs
Barbara S
BS
Borden
Ernest C
EC
Lindner
Daniel J
DJ
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002455:Cell Division / Q000187:drug effects; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D013792:Thalidomide / Q000008:administration & dosage*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D013792:Thalidomide; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a