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木犀草素逆转由TGF-β1诱导的人肺癌细胞上皮-间充质转化的实验研究 预览

Effect of luteolin on TGF-β1-induced epithelial-mesenchymal transition in lung cancer A549 cells
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摘要 目的:探讨在肺癌A549细胞中木犀草素(luteolin)对转化生长因子β1(transforming growth factor-β1, TGF-β1)诱导的上皮-间充质转化(epithelial-mesenchymal transition, EMT)及细胞侵袭的影响。方法:将不同浓度(5、10、20、40、80和160μmol/L)的luteolin作用于肺癌A549细胞后,采用四甲基偶氮唑盐(MTT)法检测细胞活力;TGF-β1诱导肺癌A549细胞建立EMT模型,加入不同浓度luteolin处理;倒置显微镜观察细胞形态的变化;Transwell小室实验检测细胞侵袭能力的变化;Western blot法检测细胞中EMT标志蛋白上皮型钙黏蛋白(E-cadherin)和波形蛋白(vimentin)的蛋白表达情况。结果:Luteolin抑制肺癌A549细胞的生长,并呈一定的时间-剂量依赖关系(P<0.05),luteolin作用24 h的IC50为68.79μmol/L,48 h的IC50为47.86μmol/L。TGF-β1诱导的肺癌A549细胞发生EMT。Luteolin显著抑制TGF-β1诱导肺癌A549细胞的侵袭能力(P<0.01)。Luteolin能逆转TGF-β1诱导的肺癌A549细胞EMT形态的改变,同时,Western blot法检测也显示luteolin可逆转TGF-β1诱导的肺癌A549细胞EMT标志蛋白E-cadherin表达的下调和vimentin表达的上调(P<0.01)。结论:Luteolin逆转TGF-β1诱导肺癌A549细胞的EMT,同时对肺癌细胞的侵袭和转移有一定的抑制作用。 AIM: To investigate the effects of luteolin on the invasion and epithelial-mesenchymal transition(EMT) induced by transforming growth factor-β1(TGF-β1) in lung cancer A549 cells. METHODS: The effect of luteolin at 5, 10, 20, 40, 80 and 160 μmol/L on the viability of A549 cells was measured by MTT assay. The invasion ability was analyzed by Transwell method. The morphological changes of the A549 cells were observed under microscope.The protein expression of E-cadherin and vimentin in the A549 cells were determined by Western blot. RESULTS: The viability of the A549 cells was significantly inhibited by luteolin in a dose-time dependent manner(P<0.05). The IC50 of luteolin for the A549 cells(24 h) was 68.79 μmol/L, while that(48 h) was 47.86 μmol/L. TGF-β1 induced morphological alteration of the A549 cells from epithelial to mesenchymal forms. Luteolin significantly inhibited TGF-β1-induced invasion of the A549 cells(P<0.01). The protein expression of E-cadherin was significantly down-regulated and the protein expression of vimentin was significantly up-regulated in the presence of TGF-β1 at 5 μg/L(P<0.01). However, luteolin reversed TGF-β1-induced EMT, up-regulation of E-cadherin and down-regulation of vimentin(P<0.01). CONCLUSION: Lu-teolin reverses TGF-β1-induced EMT in the lung cancer A549 cells.
作者 缪存静 陈俊杰 历星 林鹏程 胡全 MIAO Cun-jing,CHEN Jun-jie,LI Xing,LIN Peng-cheng,HU Quan(Department of Pharmacy,Sir Run Run Shaw Hospital Affiliated to School of Medicine,Zhejiang University,Hangzhou 310018,China;Department of Pulmonary and Critical Care Medicine,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou 32500,China;Department of Pharmaceutical Sciences,School of Medicine,Hangzhou Normal University,Hangzhou310036,China)
出处 《中国病理生理杂志》 CAS CSCD 北大核心 2019年第7期1163-1168,共6页 Chinese Journal of Pathophysiology
基金 国家自然科学基金资助项目(No.51472067) 浙江省医药卫生科技项目(No.2017187846) 浙江省医药卫生科技项目(No.2015KYB246).
关键词 转化生长因子Β1 上皮-间充质转化 木犀草素 肺癌 细胞侵袭 Transforming growth factor-β1 Epithelial-mesenchymal transition Luteolin Lung cancer Cell invasion
作者简介 通讯作者:胡全,Tel:057128865673;E-mail:huq0203@163.com。
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