Wnt蛋白生成抑制剂2对非小细胞肺癌细胞迁移与侵袭能力的影响  

Effects of the inhibitor of Wnt production 2 on cell migration and invasion in non-small cell lung cancer

作　　者：张静[1] 滕宇[1] 赵晓婷[1] 江妹[1] 岳文涛[1] 

机构地区：[1]首都医科大学附属北京胸科医院/北京市结核病胸部肿瘤研究所细胞生物学研究室,北京101149

出　　处：《癌变．畸变．突变》2017年第4期245-250,共6页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：国家自然科学基金(81672838;81602531)

摘　　要：目的:探讨Wnt蛋白生成抑制剂2(the inhibitor of Wnt production 2,IWP2)对非小细胞肺癌细胞迁移与侵袭能力的影响。方法:体外培养非小细胞肺癌H1299和95C细胞,分为对照组(无血清培养基)及实验组(应用10μmol/L IWP2处理24或48 h)。采用划痕实验和未铺Matrigel胶的Transwell迁移实验检测IWP2对细胞迁移能力的影响;铺有Matrigel胶的Transwell侵袭实验检测IWP2对细胞侵袭能力的影响;Western blot实验检测IWP2对非小细胞肺癌细胞中β-catenin及上皮间充质转化(EMT)相关蛋白ZEB1、Snail表达的影响。结果:划痕实验结果显示,经10μmol/L IWP2处理24 h后,与对照组比较,实验组H1299和95C细胞的划痕愈合面积均明显降低(P<0.01);在Transwell迁移实验中,实验组过膜细胞数明显降低(P<0.01);Transwell侵袭实验结果显示,实验组细胞表现出更低的侵袭能力(P<0.01)。Western blot结果表明,H1299和95C细胞在经IWP2作用后,与对照组比较,β-catenin的表达水平分别降低41.3%和36.1%(P均<0.01);IWP2也抑制了EMT相关蛋白ZEB1、Snail的表达,与对照组比较,实验组H1299和95C细胞中,ZEB1的表达水平分别降低51.8%和40.9%,Snail表达水平分别降低43.2%和30.7%,差异均具有统计学意义(P均<0.01)。结论:IWP2抑制β-catenin的表达并抑制非小细胞肺癌细胞发生EMT,从而降低细胞的迁移与侵袭能力。OBJECTIVE：To investigate the role of the inhibitor of Wnt production 2 （IWP2） on non-small cell lung cancer （NSCLC） cell migration and invasion and to explore mechanisms for the effects.METHODS：H1299 and 95C cell lines were divided into control （cultured with serum-free RPMI-1640 media） and experiment （treated with 10μmol/L IWP2） groups. Cell migration ability was examined with wound healing and with Transwell assay without Matrigel. Cell invasion ability was determined using Transwell assay with Matrigel. In addition,Western blot was performed to analyze the effect of IWP2 onβ-catenin and epithelial-mesenchymal transition（EMT）-related proteins （ZEB1 and Snail）. RESULTS：Compared with the control groups,the wound healing results demonstrated that cells cultured with IWP2 had decreased wound closure both in H1299 and 95C （P〈0.01）. Transwell assay without Matrigel showed that fewer cells migrated to the lower chambers after being treated with IWP2 （P〈0.01）. The Transwell assay with Matrigel indicated that cell invasion ability was also significantly decreased in the experimental compared with the control groups. Besides,after being treated with IWP2,expression of β-catenin was obviously reduced （41.3% in H1299 and 36.1% in 95C）. In addition,IWP2 also decreased the expression of ZEB1 （51.8% in H1299 and 40.9% in 95C） and Snail （43.2% in H1299 and 30.7% in 95C）.CONCLUSION：Our study revealed that IWP2 down-regulated EMT via blockingβ-catenin which led to the inhibition of NSCLC cell migration and invasion.

关 键 词：Wnt蛋白生成抑制剂2 非小细胞肺癌 迁移 侵袭 Β-CATENIN 

分 类 号：R734.2[医药卫生—肿瘤]