下调转化生长因子β激活激酶1抑制胰腺神经内分泌肿瘤转移和侵袭  

Downregulation of transforming growth factorβ-activated kinase 1 inhibits the metastasis and invasion of pancreatic neuroendocrine neoplasms

作　　者：杨晓玉[1] 柏建安 孙诚 汤琪云[2] YANG Xiaoyu;BAI Jian’an;SUN Cheng;TANG Qiyun(Department of Gastroenterology,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029;Department of Geriatric Medicine,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029;Jiangsu Key Laboratory of Neuroregeneration,Nantong University,China)

机构地区：[1]南京医科大学第一附属医院消化科,江苏南京210029 [2]南京医科大学第一附属医院老年消化科,江苏南京210029 [3]南通大学神经再生重点实验室

出　　处：《胃肠病学和肝病学杂志》2020年第4期406-410,共5页Chinese Journal of Gastroenterology and Hepatology

基　　金：江苏省“333”工程项目(BRA2017535)。

摘　　要：目的探究转化生长因子β激活激酶1(TAK1)在胰腺神经内分泌肿瘤(p-NENs)进展中的作用与影响。方法采用实时定量荧光聚合酶链反应(qRT-PCR)和蛋白印迹法(Western blotting)检测p-NENs细胞株(BON-1)、人正常胰腺导管上皮细胞系(hTERT-HPNE)和人胰腺导管腺癌细胞系(CFPAC-1)中TAK1表达情况。采用靶向TAK1的短发夹RNA(shRNA),以慢病毒为载体对BON-1进行基因敲降。通过四甲基偶氮唑蓝(MTT)法和EdU实验观察细胞增殖活力,Transwell实验观察细胞侵袭与迁移能力变化,Western blotting检测上皮间质转化(epithelial-mesenchymal transition,EMT)相关标志性蛋白表达。结果BON-1中TAK1 mRNA和蛋白质水平的表达相较于hTERT-HPNE和CFPAC-1明显升高(P<0.05),抑制BON-1中TAK1的表达后,细胞的增殖能力无明显变化,但细胞的迁移和侵袭能力明显减弱(P<0.05)。与对照组相比,敲降组的EMT相关蛋白中,上皮细胞标志性蛋白E-cadherin表达升高,间质细胞标志性蛋白Vimentin和N-cadherin表达明显降低(P<0.05)。结论在BON-1中,抑制TAK1的表达能够抑制肿瘤细胞的EMT过程,降低细胞的迁移和侵袭能力,从而抑制p-NENs的进展。Objective To investigate the function of transforming growth factorβ-activated kinase 1(TAK1)on the progression of pancreatic neuroendocrine neoplasms(p-NENs).Methods Quantitative real time fluorescence polymerase chain reaction(qRT-PCR)and Western blotting were performed to detect TAK1 expression of p-NENs cells(BON-1),human normal epithelial cells of pancreas(hTERT-HPNE)and human pancreatic cancer cells(CFPAC-1).Short hairpin RNA(shRNA)was transfected on BON-1 to downregulate the expression of TAK1,and then cell proliferation was detected by MTT and EdU assay.The migratory and invasive ability of cells were detected by transwell assay.Western blotting was used to detect the expression of epithelial-mesenchymal transition(EMT)related protein.Results The expressions of TAK1 mRNA and protein in BON-1 were significantly increased compared with hTERT-HPNE and CFPAC-1(P<0.05).After inhibiting the expression of TAK1 in BON-1,it had no obvious effect on the proliferation of cells,but the migratory and invasive abilities of cells were significantly repressed compared with the control group(P<0.05).Moreover,in the knockdown group,the expression of epithelial marker E-cadherin was increased,while mesenchymal marker Vimentin and N-cadherin were significantly decreased(P<0.05).Conclusion The silence of TAK1 could significantly attenuate the process of EMT,and inhibit the migration and invasion of BON-1.Therefore,targeting against TAK1 is likely as a potential therapeutic strategy for the treatment of p-NENs.

关 键 词：转化生长因子β激活激酶1 侵袭 迁移 胰腺神经内分泌肿瘤 上皮间质转化 

分 类 号：R735[医药卫生—肿瘤]