Bauer Joseph A, Morrison Bei H, Grane Ronald W, Jacobs Barbara S, Borden Ernest C, Lindner Daniel J
Taussig Cancer Center, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
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.
血管生成是肿瘤生长和转移的绝对必要条件。本研究的目的是评估干扰素-α2b（IFN-α2b）和沙利度胺作为单一药物及联合用药时的抗血管生成活性。采用小鼠真皮模型评估裸鼠体内肿瘤诱导的血管生成。将人ACHN（肾）、NIH-OVCAR-3（卵巢）、LNCaP（前列腺）和SK-Mel-1（黑色素瘤）肿瘤细胞皮内接种到裸鼠侧腹。每天给药的IFN-α2b和沙利度胺是所有四种肿瘤类型诱导的血管生成的有效抑制剂。在体外对IFN-α2b和沙利度胺的抗增殖作用耐药的肿瘤中，IFN-α2b和沙利度胺联合用药使平均血管计数协同减少。这种对血管生成的增强抑制在异种移植模型中转化为协同抗肿瘤活性。聚乙二醇化干扰素-α（PEG-IFN-α2b）（10^6 U）每10天给药一次与每天给予IFN-α2b治疗（10^6 U×10天）效果相同。IFN-α2b和沙利度胺联合使用时具有增强的抗血管生成活性。单剂量的PEG-IFN-α2b（10^6 U）在抑制血管生长方面与每天给予等量IFN-α2b持续10天的效果相同。
