干扰素α亚型对人肝癌细胞系的生长抑制作用因细胞系而异。

Growth inhibitory effects of interferon-alpha subtypes vary according to human liver cancer cell lines.

作者信息

Yano Hirohisa, Yanai Yoshiaki, Momosaki Seiya, Ogasawara Sachiko, Akiba Jun, Kojiro Sakiko, Moriya Fukuko, Fukahori Suguru, Kurimoto Masashi, Kojiro Masamichi

机构信息

Department of Pathology, Kurume University School of Medicine, Research Center of Innovative Cancer Therapy of the 21st Century COE Program for Medical Science, Kurume University, Kurume, Fukuoka, Japan.

出版信息

J Gastroenterol Hepatol. 2006 Nov;21(11):1720-5. doi: 10.1111/j.1440-1746.2006.04357.x.

DOI:10.1111/j.1440-1746.2006.04357.x

PMID:16984596

Abstract

BACKGROUND

Interferon (IFN)-alpha preparations used in the treatment of viral and neoplastic disease consist of single or multiple IFN-alpha subtypes that may possess different biological activity, but there are no data on liver cancer cells.

METHODS

Antiproliferative effects and the mechanisms of growth inhibition of five IFN-alpha subtypes (alpha1, alpha2, alpha5, alpha8 and alpha10) were examined in vitro using 13 human liver cancer cell lines.

RESULTS

The antiproliferative effect of each IFN-alpha subtype was different in each cell line. The 50% growth inhibitory concentration (IC50) on an antiviral unit basis showed that alpha5 presented the most potent antiproliferative effects in 11 of the 13 cell lines, and alpha8 in two cell lines. On average, the antiproliferative effects were strong in descending order from alpha5, alpha8, alpha10, alpha2 to alpha1. On weight basis, the most potent antiproliferative effect was shown by alpha8 in nine of the 13 cell lines, alpha5 in four cell lines, and the potency of the effects on average in descending order was alpha8, alpha5, alpha10, alpha2 and alpha1. No significant difference was observed between natural and recombinant alpha2. The mechanism of growth inhibition of each subtype in HAK-1B and KMCH-1 cell lines were apoptosis and S-phase arrest, and their induction levels were related to a certain degree to the antiproliferative effects.

CONCLUSIONS

Our findings show that the antiproliferative effect of each IFN-alpha subtype varies according to the cell line, but that the cells are relatively or absolutely responsive to alpha5 and alpha8 subtypes.

摘要

背景

用于治疗病毒和肿瘤疾病的干扰素（IFN）-α制剂由单一或多种IFN-α亚型组成，这些亚型可能具有不同的生物学活性，但尚无关于肝癌细胞的相关数据。

方法

使用13种人肝癌细胞系在体外检测5种IFN-α亚型（α1、α2、α5、α8和α10）的抗增殖作用及生长抑制机制。

结果

每种IFN-α亚型在各细胞系中的抗增殖作用不同。以抗病毒单位计算的50%生长抑制浓度（IC50）显示，α5在13种细胞系中的11种中呈现出最强的抗增殖作用，α8在2种细胞系中作用最强。平均而言，抗增殖作用从强到弱依次为α5、α8、α10、α2、α1。以重量计算，α8在13种细胞系中的9种中呈现出最强的抗增殖作用，α5在4种细胞系中作用最强，平均作用强度从强到弱依次为α8、α5、α10、α2、α1。天然α2和重组α2之间未观察到显著差异。HAK-1B和KMCH-1细胞系中各亚型的生长抑制机制为凋亡和S期阻滞，其诱导水平与抗增殖作用在一定程度上相关。