论文部分内容阅读
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。
Objective To investigate the effect of hypoxia-induced metallothioneins (MTs) on the epithelial-mesenchymal transition (EMT) in papillary thyroid carcinoma (PTC). Methods Human papillary thyroid carcinoma (NPA) cells were divided into normal oxygen group (21% O2), hypoxia group (5% O2) and MTs-siRNA interfered hypoxia group. Western blot and RT- The expressions of MTs, E-cadherin and Vimentin in each group were detected. The number of invasion and metastasis cells in each group was detected by Transwell / Matrigel. Results Hypoxia induced the expression of MTs in NPA cells, accompanied by the down-regulation of E-cadherin expression and Vimentin expression. The number of invasive cells increased from 15.6 ± 2.8 to 40.3 ± 5.1 in normal oxygen group. The number of migrating cells was 25.1 ± 5.6 to 48.7 ± 7.6, respectively (all P <0.01). The targeted interference of MTs could inhibit the hypoxia-induced MTs protein expression, the expression of E-cadherin, the decrease of Vimentin expression and the number of invasive cells Increased to 25.7 ± 4.2, the number of migrating cells increased to only 35.5 ± 5.4, which was significantly different from that in hypoxia group (P <0.05). Conclusions MTT induced by hypoxia can promote the EMT of human PTC cells. The targeted inhibition of MTs can partially suppress EMT.