文章摘要
聂兆超,石 星,毛海婷.IL⁃18诱导的单核细胞THP⁃1对肺癌细胞增殖、迁移和侵袭的影响[J].南京医科大学学报,2019,(10):1430~1436
IL⁃18诱导的单核细胞THP⁃1对肺癌细胞增殖、迁移和侵袭的影响
Effects of IL⁃18⁃induced mononuclear cell THP⁃1 on proliferation,migration and invasion of lung cancer cells
投稿时间:2018-10-18  
DOI:10.7655/NYDXBNS20191005
中文关键词: 肺癌细胞  THP⁃1  IL⁃18  EMT
英文关键词: lung cancer cells  THP⁃1  IL⁃18  EMT
基金项目:山东省自然科学基金(ZR201807060425)
作者单位
聂兆超 山东大学第二医院检验医学中心山东 济南 250000 
石 星 淄博市妇幼保健院检验科山东 淄博 255000 
毛海婷 山东大学第二医院检验医学中心山东 济南 250000 
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中文摘要:
      目的:探讨外源性白介素18(interleukin 18,IL?18)对单核细胞THP?1的活化作用以及IL?18激活诱导的THP?1对肺癌A549细胞增殖、迁移和侵袭的影响。方法:通过IL?18体外诱导THP?1模拟激活体内肿瘤微环境中的肿瘤相关巨噬细胞(tumor associated macrophage,TAM)的作用。Transwell法检测IL?18对单核细胞THP?1的趋化作用;外源性IL?18刺激THP?1细胞后流式细胞术检测M1、M2型TAM的比例;IL?18激活诱导的THP?1和肺癌细胞A549共培养,分别以克隆形成实验、细胞划痕实验、细胞侵袭实验检测共培养后A549细胞增殖、迁移和侵袭的变化;扫描电镜观察共培养后A549细胞形态的变化;qRT?PCR和Western blot检测共培养后A549细胞上皮间质转化(epithelial mesenchymal transition,EMT)标志蛋白E?cadherin和N?cadherin、Snail以及Slug的表达。结果:IL?18对THP?1细胞具有显著的趋化作用;外源性IL?18刺激THP?1细胞表型向M2 TAM方向分化;IL?18诱导THP?1促进了A549细胞增殖、迁移和侵袭能力;扫描电镜结果显示IL?18诱导THP?1促进A549细胞伪足生长;qRT?PCR和Western blot检测结果显示经IL?18诱导的THP?1抑制A549细胞E?cadherin的表达,促进N?cadherin、Snail以及Slug的表达,说明IL?18诱导THP?1激活A549细胞发生EMT。结论:IL?18可以诱导THP?1并促进其活化,活化后的THP?1通过激活EMT机制促进肺癌A549细胞的增殖、迁移和侵袭。
英文摘要:
      Objective:To investigate the activation of monocytes(THP?1)by exogenous interleukin 18(IL?18)and the proliferation,metastasis and invasion of lung cancer A549 cells by THP?1 induced by IL?18 activation influences. Methods:The role of tumor associated macrophages(TAMs)in tumor microenvironment in vivo was simulated by IL?18 induced THP?1 in vitro. The chemotactic effect of IL?18 on mononuclear cell THP?1 was detected by Transwell method. Exogenous IL?18 stimulated THP?1 cells and detected the proportion of M1 and M2 TAMs;IL?18?activated TAMs and lung cancer cells A549 were co?cultured. The changes of proliferation,migration and invasion of co?cultured A549 cells were detected by cloning experiment,cell scratch test and cell invasion assay. The morphology of A549 cells after co?culture was observed by scanning electron microscope. The expressions of epithelial mesenchymal transition(EMT)marker proteins E?cadherin,N?cadherin,Snail and Slug in A549 cells were detected by qRT?PCR and Western blot. Results:IL?18 had a significant chemotactic effect on THP?1 cells. Exogenous IL?18 stimulated the THP?1 cell phenotype from M2 to TAMs. IL?18 induced THP?1 promoted the proliferation,migration and invasion of A549. Scanning electron microscopy showed that THP?1 promoted the growth of pseudopod of A549 cells. At the same time,the expression of E?cadherin was inhibited,and the expression of N?cadherin,Snail and Slug was promoted,indicating that IL?18 induced THP?1 activated EMT in A549 cells. Conclusion:In lung cancer,IL?18 can activate THP?1 and promote their activation. Activated THP?1 promotes the proliferation,migration and invasion of lung cancer A549 cells by activating EMT.
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