李 优,王 剑,牟 好.姜黄素通过PI3K/AKT/mTOR通路抑制TGF-β1诱导的肺癌细胞上皮间质转化[J].肿瘤学杂志,2016,22(8):607-614.
姜黄素通过PI3K/AKT/mTOR通路抑制TGF-β1诱导的肺癌细胞上皮间质转化
Curcumin Inhibits TGF-β1-induced Epithelial-mesenchymal Transition of Lung Adenocarcinoma Cells via PI3K/AKT/mTOR Signaling Pathway
投稿时间:2016-03-20  
DOI:10.11735/j.issn.1671-170X.2016.08.B001
中文关键词:  姜黄素  肺肿瘤  上皮间质转化  TGF-β1
英文关键词:curcumin  lung neoplasms  epithelial-mesenchymal transition  transforming growth factor β1
基金项目:南京军区医学科技创新项目(15MS158);浙江省科技厅公益性技术应用研究计划(2014C33277);杭州市科技发展计划项目(20130633B29,20140633B40)
作者单位
李 优 浙江中医药大学第二临床医学院 
王 剑 解放军第一一七医院 
牟 好 浙江中医药大学第二临床医学院 
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中文摘要:
      摘 要:[目的] 探讨姜黄素对TGF-β诱导的肺癌A549细胞上皮间质转化、侵袭转移的影响及其可能的机制。[方法] 通过转化生长因子TGF-β1诱导肺癌细胞株A549发生上皮间质转化;利用不同浓度姜黄素干预由TGF-β1诱导的肺癌 A549细胞,倒置显微镜观察细胞形态变化,细胞划痕实验、Transwell 侵袭实验检测细胞迁移及侵袭能力变化,Western blot法检测上皮表型标记蛋白E-cadherin和间质表型标记蛋白N-cadherin、Vimentin的表达及PI3K/AKT/mTOR信号通路中AKT、mTOR磷酸化的情况,并利用PI3K抑制剂LY290004、mTOR抑制剂Rapamycin通过上述方法对姜黄素的作用进行印证。[结果] 与对照组相比,姜黄素显著增加A549细胞E-cadherin的表达,抑制N-cadherin和Vimentin蛋白及TGF-β1刺激p-AKT和p-mTOR的表达,且呈明显的剂量—时间依赖关系;同时抑制TGF-β诱导的侵袭迁移。[结论] 姜黄素可通过PI3K/AKT/mTOR通路明显抑制TGF-β1诱导的肺癌A549细胞上皮间质转化,降低其侵袭迁移能力。
英文摘要:
      Abstract:[Objective] To investigate the effect of curcumin on TGF-β1-induced epithelial-mesenchymal transition,invasion and migration of lung cancer A549 cells,and the potential mechanism. [Methods] Different concentrations of curcumin were used to intervene the TGF-β1 treated lung cancer A549 cells. The morphological changes were observed under inverted microscope;wound Healing assay and Transwell assay were used to observe the changes if invasion and migration ability of A549 cells;Western blot was used to analyze the expression of epithelial phenotype marker protein E-cadherin,mesenchymal phenotype marker protein N-cadherin,Vimentin and the phosphorylation of transcription factor AKT,mTOR in PI3K/AKT/mTOR signaling pathway. PI3K inhibitors and mTOR inhibitors were applied to conform the affects of curcumin.[Results] Compared with controls,curcumin inhibited the invasion and migration of TGF-β1-induced A549 cell;decreased the expression of N-cadherin,Vimentin;increased the expression of E-cadherin;suppressed the expression of p-AKT and p-mTOR stimulated by TGF-β1,in a dose and time-dependent manner.[Conclusion] Curcumin can inhibit TGF-β1-induced epithelial-mesenchymal transition of lung adenocarcinoma cells,in which PI3K/AKT/mTOR signaling pathway may be involved.
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