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

Daintain/AIF-1 accelerates the activation of insulin-like growth factor-1 receptor signaling pathway in HepG2 cells
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Daintain/AIF-1 加速 HepG2 细胞中胰岛素样生长因子-1 受体信号通路的激活

DOI:
10.3892/or.2015.4002
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发表时间:
2015-07-01
期刊:
影响因子:
4.2
通讯作者:
Chen, Ning
Chen, Ning
中科院分区:
医学3区
文献类型:
--
作者:
Jia, Shaohui;Du, Zhongxia;Chen, Ning

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Daintain/同种异体移植炎症因子-1(AIF-1)是一种新的炎症因子,具有促进乳腺癌细胞增殖和迁移的作用。然而,Daintain/AIF-1在肝癌发生中的作用尚不清楚。为探讨DAIN/AIF-1在肝细胞癌发生发展中的作用,采用酶联免疫吸附试验(ELISA)和逆转录聚合酶链式反应(RT-PCR)检测肝细胞癌组织中胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子-2(IGF-2)和胰岛素样生长因子结合蛋白-3(IGFBP-3)的分泌和基因表达。免疫印迹法检测IGF-1R及其下游靶点的表达。采用四甲基偶氮唑盐(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylterazolium)比色法和流式细胞仪检测细胞增殖和细胞周期变化。结果显示,Daintain/AIF-1处理后的HepG2细胞IGF-1和IGF-2分泌明显增加,IGFBP-3分泌减少。此外,Daintain/AIF-1可促进IGF-1诱导的IGF-1R及其下游AKT信号通路的激活,进而促进细胞周期蛋白D1通路的激活,从而加快细胞周期进程,最终促进细胞增殖。综上所述,Daintain/AIF-1通过促进IGF-1R及其下游信号通路的激活而促进了HepG2细胞的增殖,证实了Daintain/AIF-1在肝细胞癌的发生发展中起着重要作用。
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.