文章摘要
张丽娟,郏文亭,兰 玲,钱 玮,杨雪阳,徐宽枫,崔 岱.二甲双胍对甲状腺未分化癌侵袭转移的影响及机制研究[J].南京医科大学学报,2017,(5):554~558
二甲双胍对甲状腺未分化癌侵袭转移的影响及机制研究
The study on the effect of metformin on invasion and metastasis of undifferentiated thyroid cancer and its underlying mechanisms
投稿时间:2017-01-07  
DOI:10.7655/NYDXBNS20170507
中文关键词: 二甲双胍  甲状腺未分化癌  侵袭  转移  上皮间质转化
英文关键词: metformin  undifferentiated thyroid cancer  invasion  metastasis  epithelial-mesenchymal transition
基金项目:江苏省“六大人才高峰”高层次人才项目(WSN-023)
作者单位
张丽娟 南京医科大学第一附属医院内分泌科江苏 南京 210029 
郏文亭 南京医科大学第一附属医院内分泌科江苏 南京 210029江苏省老年医院内科江苏 南京 210024 
兰 玲 北京积水潭医院内分泌科北京 100035 
钱 玮 南京医科大学第一附属医院内分泌科江苏 南京 210029 
杨雪阳 南京医科大学第一附属医院内分泌科江苏 南京 210029 
徐宽枫 南京医科大学第一附属医院内分泌科江苏 南京 210029 
崔 岱 南京医科大学第一附属医院内分泌科江苏 南京 210029 
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中文摘要:
      目的:研究二甲双胍对甲状腺未分化癌侵袭转移能力的影响,初步探讨其作用机制。方法:以不同浓度的二甲双胍处理甲状腺未分化癌细胞株SW1736,分别通过琼脂滴法及Transwell侵袭迁移实验,对比观察二甲双胍组与对照组SW1736细胞的侵袭转移能力,real-time PCR方法检测细胞中与上皮间质转化(epithelial-mesenchymal transition,EMT)过程密切相关的分子,包括波形蛋白(vimentin)、E-钙黏素(E-cadherin)、转录因子Snail1及Slug mRNA表达变化。结果:琼脂滴法及Transwell侵袭迁移实验均发现二甲双胍可降低SW1736细胞体外侵袭迁移能力,且随二甲双胍浓度的增高,其抑制作用增强;二甲双胍可显著下调甲状腺未分化癌细胞中vimentin及转录因子Slug和Snail1表达,促进上皮细胞表型E-cadherin表达。结论:二甲双胍可通过下调Snail1和Slug的表达促进E-cadherin 的表达,从而抑制EMT过程,降低甲状腺癌细胞侵袭迁移能力,为甲状腺癌的治疗提供新思路。
英文摘要:
      Objective:To observe the effects of metformin on the invasion and metastasis of undifferentiated thyroid cancer and to evaluate its underlying mechanisms. Methods:The undifferentiated thyroid cancer cell line SW1736 was treated with different concentrations of metformin. The invasive and metastatic abilities of SW1736 cells were measured by agar drop method and Transwell invasion and migration assay. Real-time PCR was used to detect the molecules mRNA involved in the process of epithelial-mesenchymal transition(EMT),including vimentin,E-cadherin and transcription factors Snail1 and Slug. Results:Metformin inhibited the invasive and migration capacities of SW1736 cells in vitro. The inhibitory effects of metformin were dose dependent. Metformin significantly down-regulated the expressions of vimentin,Slug and Snail1 in SW1736 cells. Meanwhile,it stimulated the expression of E-cadherin,which highly expresses in epithelial cells. Conclusion:Metformin can promote the expression of E-cadherin by down-regulating the expression of Snail1 and Slug,thus inhibiting the process of EMT and decreasing the invasive and migration ability of thyroid carcinoma,which may provide a novel strategy for the treatment of thyroid neoplasms.
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