下调HER2降低自噬活性抑制人肺癌细胞增殖转移作用的体外研究  

The inhibition of autophagy suppresses proliferation and metastasis of lung cancer cells via down-regulation of HER2

作　　者：冯媛媛[1] 伍宏山 张志宏[2] 龙新华[2] 周扬[2] 童未来 刘志礼[2] 刘家明[2] 

机构地区：[1]南昌大学基础医学部,330006 [2] 南昌大学第一附属医院骨科

出　　处：《天津医药》2016年第11期1330-1333,共4页Tianjin Medical Journal

基　　金：江西省自然科学基金项目(2014ZBAB205012,20151BAB215026)

摘　　要：目的探讨下调HER2表达是否抑制细胞自噬活性,从而影响人肺癌细胞的增殖、迁徙和侵袭。方法采用浓度5μmol/L自噬抑制剂3-MA、10μmol/L HER2抑制剂Neratinib分别作用人肺癌细胞A549。Western blot检测肺癌细胞A549中HER2、Beclin-1及LC3B(Ⅱ/Ⅰ)蛋白表达水平;Wound healing和Transwell invasion实验检测细胞迁徙、侵袭能力;四甲基偶氮唑盐(MTT)检测细胞的增殖能力。结果 Neratinib和自噬抑制剂(3-MA)作用24 h后,细胞HER2、Beclin-1及LC3B(Ⅱ/Ⅰ)蛋白表达水平显著低于阴性对照组;Neratinib、自噬抑制剂(3-MA)处理组的细胞增殖、迁徙和侵袭能力显著低于阴性对照细胞。结论下调HER2能降低人肺癌细胞A549的自噬活性并抑制其增殖、迁徙和侵袭。Objective To investigate whether the down-regulation of HER2 can inhibit the autophagy of cells andinfluence the proliferation and metastasis of lung cancer cells. Methods The 5 μmol/L of autophagy inhibitor(3-MA) and10 μmol/L of HER2 inhibitor(Neratinib) were used to treat human lung cancer A549 cells. Western blot assay was used todetect the protein expressions of HER2, Beclin-1 and LC3B(Ⅱ/Ⅰ) in A549 cells. Wound healing and Transwell invasionmethods were used to detect the invasion and migration ability of A549 cells. MTT assay was performed to evaluate the cellproliferation. Results Western blot analysis showed that the protein expressions of HER2, Beclin-1 and LC3B(Ⅱ/Ⅰ)were significantly declined in A549 cells treated with Neratinib and 3-MA for 24 h compared to cells in control group. Thecell proliferation, migration and invasion ability were significantly decreased in A549 cells treated with Neratinib and 3-MAthanthoseofcontrolcells.Conclusion Theinhibitionof HER2 proteincansuppresstheautophagyandproliferationof A549cells.

关 键 词：肺肿瘤 自噬 细胞增殖 受体 erbB-2 细胞侵袭 细胞迁徙 

分 类 号：R734.2[医药卫生—肿瘤]