Cereblon在沙利度胺抑制人肺腺癌A549细胞迁移中的作用  

Effect of cereblon on inhibition of human lung cancer A549 cell migration by thalidomide

作　　者：黄海宁 龙超良 张浩 汪海[2,3] HUANG Hai-ning;LONG Chao-liang;ZHANG Hao;WANG Hai(Affiliated Hospital of Jining Medical University,Jining 272029,China;Thadweik Academy of Medicine,Beijing 100039,China;General Hospital of PLA,Beijing 100853,China)

机构地区：[1]济宁医学院附属医院,济宁272029 [2]北京赛德维康医药研究院,北京100039 [3]中国人民解放军总医院,北京100853

出　　处：《国际药学研究杂志》2019年第8期591-596,共6页Journal of International Pharmaceutical Research

基　　金：济宁医学院附属医院“苗圃”项目(MP-2018-006)

摘　　要：目的探讨cereblon(CRBN)蛋白在沙利度胺抑制人肺腺癌A549细胞迁移中的作用及其机制。方法用MTS法检测沙利度胺对A549细胞增殖的影响;用RNA干扰(RNAi)及慢病毒感染法,研究建立稳定敲低CRBN的A549细胞株(A549CRBN);Transwell实验检测沙利度胺对A549和A549CRBN细胞迁移的影响;用实时定量PCR方法,检测细胞迁移相关分子神经型钙黏蛋白(N-cadherin)和波形蛋白(vimentin)的基因表达水平。结果沙利度胺在浓度分别为1、10、50、100μmol/L时均不影响A549细胞的增殖能力,但100μmol/L时能显著抑制A549细胞的迁移能力(P<0.05);敲低CRBN后,A549CRBN细胞的迁移能力显著降低(P<0.01),且其N-cadherin和vimentin mRNA表达水平也显著降低(P<0.01);敲低CRBN后,沙利度胺对A549CRBN细胞迁移无显著抑制作用,其可能以CRBN依赖方式抑制N-cadherin和vimentin的表达。结论沙利度胺可能通过CRBN抑制A549细胞的迁移及其迁移相关基因的表达水平。Objective To investigate the influence of cereblon(CRBN)on the inhibitory effect of thalidomide on the migration of human lung adenocarcinoma A549 cells and related mechanism. Methods The effect of thalidomide on the A549 cell proliferation was assayed by the MTS method. CRBN in A549 cells was knocked down(A549 CRBNcells)with RNA interference and lentivirus infection. Transwell assay was performed to detect the effect of thalidomide on the cell migration of A549 and A549 CRBNcells. RT-qPCR assay was performed to detect the gene expression of N-cadherin and vimentin. Results The thalidomide at the 1,10,50 and 100 μmol/L concentration did not affect the proliferation of A549 cells,while the 100 μmol/L thalidomide could significantly inhibit the migration of A549 cells. After the CRBN gene knockdown the migration ability of A549 cells was significantly decreased(P<0.01),and the gene expression of Ncadherin and vimentin was also significantly reduced in the A549 CRBNcells. The inhibitory effect of thalidomide on the cell migration in the A549 cells disappeared after CRBN gene knockdown. Thalidomide could inhibit the gene expression of N-cadherin and vimentin in a CRBN-dependent manner. Conclusion Thalidomide could inhibit the migration of A549 cells and the expression of the migration-related genes via CRBN.

关 键 词：沙利度胺 人肺腺癌A549细胞 细胞迁移 cereblon(CRBN) 

分 类 号：R966[医药卫生—药理学]