• 首页
  • 期刊介绍
  • 编委会
  • 投稿指南
  • 期刊订阅
  • 广告合作
  • 留言板
  • 联系我们
  • English
华海侠,刘瑞吉,于晓麟,赵敏.靶向HDAC6 信号抑制非小细胞肺癌A549 细胞上皮-间质转化的机制[J].中国比较医学杂志,2019,29(8):61~67.
靶向HDAC6 信号抑制非小细胞肺癌A549 细胞上皮-间质转化的机制
Inhibition of histone deacetylase 6 signaling attenuates epithelial-mesenchymal transition in non-small cell lung cancer A549 cells
投稿时间:2019-06-05  
DOI:10.3969/j. issn. 1671 -7856. 2019. 08. 010
中文关键词:  非小细胞肺癌  上皮间质转化  组蛋白去乙酰化酶  Rho 相关卷曲螺旋激酶  细胞外信号调节激酶
英文关键词:non-small cell lung cancer (NSCLC)  epithelial-mesenchymal transition (EMT)  histone deacetylase 6(HDAC6)  rho-associated protein kinase(ROCK)  extracellular signal-regulated kinases(ERK)
基金项目:
作者单位E-mail
华海侠 肿瘤内科
秦皇岛市第一医院,河北秦皇岛 063000 
huahaixia1977@ sina.com 
刘瑞吉 呼吸内科
秦皇岛市第一医院,河北秦皇岛 063000 
12327696@ qq.com 
于晓麟 肿瘤内科
秦皇岛市第一医院,河北秦皇岛 063000 
 
赵敏 病理科
秦皇岛市第一医院,河北秦皇岛 063000 
 
摘要点击次数: 154
全文下载次数: 43
中文摘要:
      目的 观察组蛋白去乙酰化酶(HDAC6)在非小细胞肺癌(NSCLC)中表达的临床意义及其靶向HDAC6 信号对A549 细胞发生上皮间质转化(EMT)的作用机制?方法 采用免疫组织化学染色法检测HDAC6 和E-钙粘蛋白(E-ca)在NSCLC 中的表达并分析其临床病理意义;采用转化生长因子(TGF)-β1 诱导A549 细胞,并予以HDAC6?Rho 相关卷曲螺旋激酶(ROCK)和细胞外信号调节激酶(ERK)信号抑制剂预处理?CCK-8 法检测细胞增殖,划痕实验检测细胞迁移能力,transwell 实验检测细胞侵袭能力,免疫印迹法检测E-cadherin?波形蛋白(vimentin)?α-平滑肌肌动蛋白(SMA)和HDAC6 的表达?结果 HDAC6 在NSCLC 组织中高表达,与分化程度和淋巴结转移关系密切,且与E-ca 表达呈负相关?TGF-β1 能够诱导A549 细胞发生EMT,即vimentin?α-SMA 表达上调,而E-ca 表达下调;予以HDAC6?ROCK 和ERK 信号抑制剂能够显著抑制该变化?结论 HDAC6 在NSCLC 发生?发展中可能起到重要的调控作用,与肿瘤的EMT 关系密切,其作用与ROCK 和ERK 信号的调控有关?
英文摘要:
      Objective To assess the clinical significance of histone deacetylase 6 (HDAC6) expression in nonsmallcell lung cancer (NSCLC) and determine the relationship between HDAC6 and the epithelial-mesenchymal transition(EMT). Methods Tumor and noncancerous peritumoral lung tissues (controls) were collected from 52 patients withNSCLC and analyzed for HDAC6 and E-cadherin expression using immunohistochemistry. Correlation analyses betweenHDAC6, E-cadherin and clinicopathological parameters were performed using χ2 tests. In vitro studies were conducted intransforming growth factor (TGF)-β1-induced A549 cells to determine the effect of HDAC6 overexpression on molecularmarkers of EMT. Results Immunohistochemical analysis revealed significantly elevated HDAC6 expression in NSCLCtissues, which correlated with the differentiation stage and lymph node metastasis. Moreover, HDAC6 expression wasinversely correlated with that of E-cadherin, an EMT marker. Treatment with an HDAC6 inhibitor and signaling inhibitors ofRho-associated protein kinase ( ROCK) or extracellular signal-regulated kinases ( ERK) significantly reduced theproliferation, migration and invasion of TGF-β1-induced A549 cells. Furthermore, western blot analysis indicated that TGF-β1 induced EMT in A549 cells, which was manifested by upregulated E-cadherin and vimentin and downregulated α-smooth muscle actin (α-SMA). Signaling inhibitors against HDAC6, ROCK and ERK reversed the effects of TGF-β1treatment. Conclusions Our data suggest that HDAC6 plays an important regulatory role in NSCLC tumorigenesis andprogression and is closely related to tumor EMT and regulation of ROCK and ERK signaling. Targeting HDAC6 activity using HDAC6, ERK1/2 or ROCK inhibitors may be a potential therapeutic option for NSCLC.
查看全文  查看/发表评论  下载PDF阅读器
关闭
您是第 2539980 位访问者
版权所有:中国实验动物学会 主管单位:中国科学技术协会 主办单位:中国实验动物学会 中国医学科学院医学实验动物研究所
地  址: 北京市朝阳区潘家园南里5号 邮编:100021 电话:010-67779337 E-mail:bjb@cnilas.org
本系统由北京勤云科技发展有限公司设计
微信关注二维码