下调TRAF6表达对肺癌细胞株恶性生物学行为的影响

被引：8

作者：

林根

黄传钟

苏光建

胡卉华

徐海鹏

黄诚

机构：

[1] 福建医科大学教学医院,福建省肿瘤医院胸部肿瘤内科

来源：

中国肺癌杂志 | 2015年 / 18卷 / 11期

关键词：

肺肿瘤; 肿瘤坏死因子受体相关因子6; 核因子-κB; 凋亡; 侵袭;

D O I：

暂无

中图分类号：

R734.2 [肺肿瘤];

学科分类号：

100117 [系统生物医学];

摘要：

背景与目的已有的研究提示肿瘤坏死因子受体相关因子6(tumor necrosis factor receptor-associated factor 6,TRAF6)在肺癌中常常扩增,可能扮演癌基因角色,但TRAF6的确切作用尚未充分阐明。本研究探索TRAF6表达对肺癌细胞株的增殖、凋亡、细胞周期、迁移及侵袭能力的影响以及可能作用机制。方法选用A549、H1650、SPC-A-1以及Calu-3等四种肺癌细胞株,应用蛋白印迹、q RT-PCR检测其TRAF6蛋白及m RNA表达。SPC-A-1、Calu-3细胞转染TRAF6 si RNA,以EMSA方法检测不同处理组核因子-κB的DNA结合活性,MTS法检测细胞增殖,流式细胞仪PI染色检测细胞凋亡,流式细胞仪进行细胞周期测定,划痕实验及Transwell小室法检测细胞迁移及侵袭能力,并应用蛋白印迹检测泛素化抗体、p65、CD24、CXCR4等蛋白表达。SPC-A-1细胞提取DNA后,应用二代测序法进行全基因组测序。结果在四种细胞株中,SPC-A-1和Calu-3细胞TRAF6相对高表达,TRAF6发生自身K63-泛素化,但仅在SPC-A-1细胞中观察到核因子-κB组成性活化。转染TRAF6 si RNA后,SPC-A-1、Calu-3细胞TRAF6表达明显下调,与空白组及对照组相比,下调TRAF6表达可抑制SPC-A-1细胞核因子-κB活性、降低迁移及侵袭能力以及促进细胞凋亡,CD24和CXCR4的表达也明显下调,但对细胞增殖及细胞周期无明显影响。下调TRAF6表达对Calu-3细胞株的核因子-κB活性、细胞增殖、凋亡、细胞周期、迁移及侵袭能力等均无明显影响。未发现SPC-A-1细胞株TRAF6基因突变或拷贝数改变。结论下调TRAF6表达可抑制SPC-A-1细胞迁移及侵袭能力,促进细胞凋亡,并且TRAF6可能是通过调控核因子-κBCD24/CXCR4信号通路参与调控肺癌侵袭、细胞凋亡。

引用

页码：661 / 667

页数：7

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