Murata Masayuki, Nabeshima Shigeki, Kikuchi Kensuke, Yamaji Kouzaburo, Furusyo Norihiro, Hayashi Jun
Department of Environmental Medicine and Infectious Disease, Internal Medicine, Faculty of Medical Science Kyushu University, and Department of General Medicine, Kyushu University Hospital, Fukuoka, Japan.
Cytokine. 2006 Feb 7;33(3):121-8. doi: 10.1016/j.cyto.2005.08.011. Epub 2006 Mar 7.
The antiviral, antiproliferative and immunomodulatory effects of type I interferons (IFNs) are well documented, however, few studies have been published concerning differences in the antitumor effects of IFN-alpha and beta. In the present study, differences in antitumor effect, including the antiproliferative effect, cell cycle change, apoptosis, and the IFN-stimulated gene (ISG) were examined by flow cytometry between IFN-alpha and beta on three human hepatocellular carcinoma (HCC) cell lines (HepG2, Huh7 and JHH4). The antiproliferative effect of both IFNs on the HCC cell lines was time- and dose-dependent, and IFN-beta was significantly stronger than IFN-alpha. The cell cycle effect by both IFNs was an S-phase accumulation, with IFN-beta having a tendency to increase the S-phase ratio more strongly than IFN-alpha, especially in Huh7. Apoptosis marker expression, Fas antigen and intracellular active caspase-3, was increased after the addition of IFNs, especially of IFN-beta. The expression of human leukocyte antigen-class I molecules, ISG-encoded protein, was increased after the addition of IFNs, especially of IFN-beta. These data suggest that IFN-beta has a greater antitumor effect than IFN-alpha on HCC of a very early stage in patients with chronic hepatitis C.
I型干扰素（IFNs）的抗病毒、抗增殖和免疫调节作用已有充分文献记载，然而，关于IFN-α和β抗肿瘤作用差异的研究报道较少。在本研究中，通过流式细胞术检测了IFN-α和β对三种人肝癌（HCC）细胞系（HepG2、Huh7和JHH4）的抗肿瘤作用差异，包括抗增殖作用、细胞周期变化、凋亡以及IFN刺激基因（ISG）。两种IFN对HCC细胞系的抗增殖作用均呈时间和剂量依赖性，且IFN-β明显强于IFN-α。两种IFN对细胞周期的影响均为S期积累，IFN-β使S期比例增加的趋势比IFN-α更强，尤其是在Huh7细胞系中。添加IFNs后，凋亡标志物Fas抗原和细胞内活性caspase-3的表达增加，尤其是IFN-β。添加IFNs后，人类白细胞抗原I类分子（ISG编码蛋白）的表达增加，尤其是IFN-β。这些数据表明，在慢性丙型肝炎患者的极早期肝癌中，IFN-β比IFN-α具有更强的抗肿瘤作用。
