中文摘要：

目的研究低氧诱导金属硫蛋白（metallothioneins,MTs）对甲状腺乳头状癌（papillary thyroid carcinoma,PTC）上皮间质转化（epithelial-mesenchymal transition,EMT）的影响。方法以人甲状腺乳头状癌NPA细胞为研究模型,将其分为正常氧组（21%O2）、低氧组（5%O2）和MTs-siRNA干扰低氧组,Western blot、RT-PCR方法检测各组细胞MTs、上皮细胞钙粘蛋白（E-cadherin）和间质细胞波形蛋白（Vimentin）的表达,Transwell/Matrigel方法检测各组细胞侵袭转移细胞数。结果低氧可诱导NPA细胞表达MTs,并伴随有EMT标志性分子E-cadherin表达的下调和Vimentin表达的升高,侵袭细胞数由正常氧组15.6±2.8增加到40.3±5.1,迁移细胞数由25.1±5.6增加到48.7±7.6,均有统计学差异（P〈0.01）;MTs靶向干扰可有效抑制低氧诱导的MTs蛋白表达,同时E-cadherin表达回升,Vimentin表达下降,侵袭细胞数仅增加到25.7±4.2,迁移细胞数仅增加到35.5±5.4,与低氧组比较均有统计学差异（P〈0.05）。结论低氧所诱导表达的MTs对人PTC细胞发生EMT有促进作用,MTs靶向干扰可使EMT受到部分抑制。

英文摘要：

Objective To determine the effects of metallothioneins（MTs） induced by hypoxia on epithelial-mesenchymal transition（EMT） in human papillary thyroid carcinoma NPA cells.Methods NPA cells were divided into 3 groups,normoxia（21% O2）,hypoxia（5% O2） and hypoxia with MTs-siRNA.The expression levels of MTs,E-cadherin and Vimentin in the 3 groups of NPA cells were analyzed by Western blotting and RT-PCR.The invasion and metastasis potential of these groups were detected by Transwell/Matrigel assay.Results Hypoxia treatment led to inducible expression of MTs,down-regulated of E-cadherin and up-regulated Vimentin at the same time,which were marker molecules of EMT in NPA cells.Meanwhile,invasive cell population of hypoxia group was increased to 40.3±5.1 from 15.6±2.8 of normoxia group（P0.01）.Migrating cell population was increased to 48.7±7.6 from 25.1±5.6 of normoxia group（P0.01）.However,the inducible expression of MTs was effectively inhibited by transfection of MTs-siRNA vector in NPA cells,followed by increased expression of E-cadherin and decreased expression of Vimentin.Moreover,invasive and migrating cell population of the hypoxia group with MTs-siRNA were only increased to 25.7±4.2 and 35.5±5.4（P0.05）.Conclusion The expression of MTs induced by hypoxia can promote EMT in human papillary thyroid carcinoma.siRNA targeting MTs can partially inhibit EMT promoted by hypoxia.