Yanai Y, Horie S, Yamamoto K, Yamauchi H, Ikegami H, Kurimoto M, Kitamura T
Fujisaki Institute, Hayashibara Biochemical Laboratories, Inc., Okayama 702-8006, Japan.
J Interferon Cytokine Res. 2001 Dec;21(12):1129-36. doi: 10.1089/107999001317205268.
Interferon-alpha (IFN-alpha) has a number of therapeutic applications in the treatment of various human cancers and diseases of viral origin. IFN-alpha includes several subtypes, and little has been reported on the biologic properties of the individual subtypes. Here, we report on the individual antitumor effects of five IFN-alpha subtypes, alpha1, alpha2, alpha5, alpha8, and alpha10, against six renal cell carcinoma (RCC) cell lines in vitro. Among the subtypes, IFN-alpha8 most potently inhibited cell proliferation and delayed the G(1)/S transition. Synergistic induction of apoptosis was shown in two of the RCC cell lines when treated with the combination of IFN-alpha and IFN-gamma rather than with either IFN-alpha or IFN-gamma alone. IFN-alpha8 was most effective in the induction of apoptosis when combined with IFN-gamma. In addition, IFN-alpha8 had the strongest ability to upregulate HLA class II antigen expression in the subtypes examined. These data indicate that subtypes of IFN-alpha have disparate antitumor effects in vitro, and in vitro distinctions among the IFN-alpha subtypes should be appreciated more in clinical application.
α干扰素(IFN-α)在治疗多种人类癌症和病毒源性疾病方面有多种治疗应用。IFN-α包括多个亚型,关于各个亚型生物学特性的报道较少。在此,我们报告了α1、α2、α5、α8和α10这五种IFN-α亚型对六种肾细胞癌(RCC)细胞系的体外抗肿瘤作用。在这些亚型中,IFN-α8最有效地抑制细胞增殖并延迟G(1)/S期转换。当用IFN-α和IFN-γ联合处理而非单独使用IFN-α或IFN-γ时,在两种RCC细胞系中显示出协同诱导凋亡的作用。IFN-α8与IFN-γ联合时诱导凋亡最有效。此外,在检测的亚型中,IFN-α8上调HLA II类抗原表达的能力最强。这些数据表明,IFN-α亚型在体外具有不同的抗肿瘤作用,在临床应用中应更多地认识到IFN-α亚型之间的体外差异。