Chen Lujun, Zhai Wensi, Zheng Xiao, Xie Quanqin, Zhou Qi, Tao Min, Zhu Yibei, Wu Changping, Jiang Jingting
Department of Tumor Biological Treatment, Changzhou, China.
Jiangsu Engineering Research Center for Tumor Immunotherapy, Changzhou, China.
Cell Physiol Biochem. 2018;45(1):15-25. doi: 10.1159/000486219. Epub 2017 Dec 22.
BACKGROUND/AIMS: The status of interferon (IFN) signaling pathway has been shown to be closely associated with the response of immune checkpoint blockade therapy against advanced human cancers. IFN-induced protein with tetratricopeptide repeats 2 (IFIT2), also known as IFN-stimulated gene 54 (ISG54), is one of the most highly responsive ISGs, which can inhibit the proliferation and migration of cancer cells, and regulate viral replication, resulting in anti-cancer and anti-viral effects. In the present study, we aimed to investigate the role of IFIT2 in human gastric cancer.
Immunohistochemistry assay was used to investigate the correlation between the IFIT2 expression in cancer tissues and clinical parameters of gastric cancer patients. Knockdown of IFIT2 was performed using RNAi to assess the role of IFIT2 in the regulation of biological behaviors in human gastric cancer cell lines.
IFIT2 expression in gastric cancer tissues was significantly associated with tumor stage and postoperative prognoses of the patients. Moreover, decreased IFIT2 expression in human gastric cancer cell lines SGC-7901 and AGS significantly increased the cell viability, cell migration and the ratios of cells in S phase.
Our present study demonstrated that the decreased IFIT2 expression could promote the gastric cancer progression and predict poor therapeutic outcomes of the patients.
背景/目的:干扰素(IFN)信号通路的状态已被证明与晚期人类癌症免疫检查点阻断治疗的反应密切相关。含四肽重复序列的IFN诱导蛋白2(IFIT2),也称为IFN刺激基因54(ISG54),是反应最强烈的ISG之一,它可以抑制癌细胞的增殖和迁移,并调节病毒复制,从而产生抗癌和抗病毒作用。在本研究中,我们旨在探讨IFIT2在人类胃癌中的作用。
采用免疫组织化学分析法研究癌组织中IFIT2表达与胃癌患者临床参数之间的相关性。使用RNA干扰技术敲低IFIT2,以评估其在调节人胃癌细胞系生物学行为中的作用。
胃癌组织中IFIT2的表达与患者的肿瘤分期和术后预后显著相关。此外,人胃癌细胞系SGC-7901和AGS中IFIT2表达的降低显著提高了细胞活力、细胞迁移能力以及S期细胞比例。
我们目前的研究表明,IFIT2表达降低可促进胃癌进展,并预示患者的治疗效果不佳。