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载脂蛋白A1/巨噬细胞迁移抑制因子-1促进肝癌细胞系HepG2中胰岛素样生长因子-1受体信号通路的激活。

Daintain/AIF-1 accelerates the activation of insulin-like growth factor-1 receptor signaling pathway in HepG2 cells.

作者信息

Jia Shaohui, Du Zhongxia, Jiang Hua, Huang Xingyuan, Chen Zhengwang, Chen Ning

机构信息

College of Health Science, Wuhan Sports University, Wuhan, Hubei 430079, P.R. China.

Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, P.R. China.

出版信息

Oncol Rep. 2015 Jul;34(1):511-7. doi: 10.3892/or.2015.4002. Epub 2015 May 20.

DOI:10.3892/or.2015.4002
PMID:25998745
Abstract

Daintain/allograft inflammatory factor-1 (AIF-1), as a novel inflammatory factor, has been reported to accelerate the proliferation and migration of breast cancer cells. However, the effect of daintain/AIF-1 on hepatocarcinogenesis remains unclear. In order to explore the effect of daintain/AIF-1 on the progression of hepatocellular carcinoma (HCC), enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR) were performed to examine the secretion and gene expression of (IGF)-1, IGF-2 and IGFBP-3. The expression of IGF-1R and its downstream targets was evaluated by western blotting. In addition, the proliferation and cell-cycle progression of HepG2 cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylterazolium bromide (MTT) and flow cytometric analysis. The results showed that HepG2 cells subjected to daintain/AIF-1 treatment revealed an obvious increase in the secretion of IGF-1 and IGF-2, and a reduction in the secretion of IGFBP-3. Moreover, daintain/AIF-1 accelerated the activation of IGF-1-induced IGF-1R and its downstream AKT signaling pathway, and subsequently promoted the activation of cyclin D1 pathway, thus accelerating the progression of the cell cycle and eventually promoting the proliferation of HepG2 cells. In conclusion, daintain/AIF-1 promoted the proliferation of HepG2 cells by accelerating the activation of IGF-1R and its downstream signaling pathway, which confirms that daintain/AIF-1 plays a crucial role in the development of HCC.

摘要

达因蛋白/同种异体移植炎症因子-1(AIF-1)作为一种新型炎症因子,据报道可加速乳腺癌细胞的增殖和迁移。然而,达因蛋白/AIF-1在肝癌发生中的作用仍不清楚。为了探究达因蛋白/AIF-1对肝细胞癌(HCC)进展的影响,采用酶联免疫吸附测定(ELISA)和逆转录聚合酶链反应(RT-PCR)检测胰岛素样生长因子(IGF)-1、IGF-2和IGFBP-3的分泌及基因表达。通过蛋白质印迹法评估IGF-1R及其下游靶点的表达。此外,采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)和流式细胞术分析评估HepG2细胞的增殖和细胞周期进程。结果显示,接受达因蛋白/AIF-1处理的HepG2细胞中,IGF-1和IGF-2的分泌明显增加,而IGFBP-3的分泌减少。此外,达因蛋白/AIF-1加速了IGF-1诱导的IGF-1R及其下游AKT信号通路的激活,随后促进了细胞周期蛋白D1通路的激活,从而加速细胞周期进程并最终促进HepG2细胞的增殖。总之,达因蛋白/AIF-1通过加速IGF-1R及其下游信号通路的激活促进了HepG2细胞的增殖,这证实达因蛋白/AIF-1在HCC的发展中起关键作用。

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