摘要
目的:研究1,25二羟维生素D_3在甲状腺未分化癌肿瘤干细胞(cancer stem cells,CSCs)的增殖及上皮细胞间质转化(epithelial-mesenchymal transition,EMT)中的作用。方法:以甲状腺未分化癌细胞株HTh74为研究对象,采用体外细胞增殖实验观察1,25二羟维生素D_3对野生型HTh74及其多柔比星耐药株的作用。采用细胞球形成实验观察1,25二羟维生素D_3对甲状腺CSCs增殖能力的作用。实时荧光定量PCR检测HTh74野生型细胞、HTh74类CSCs以及1,25二羟维生素D_3干预后的HTh74类CSCs中EMT相关基因的表达。结果:1,25二羟维生素D_3抑制HTh74野生型和多柔比星耐药株细胞的增殖,并且对耐药株具有更明显的生长抑制作用。1,25二羟维生素D_3抑制HTh74类CSCs的增殖,并显著下调HTh74类CSCs中EMT相关基因N-钙黏蛋白和Slug的表达(P<0.05)。E-钙黏蛋白在HTh74类CSCs中未检出。结论:1,25二羟维生素D_3抑制甲状腺CSCs的增殖,并抑制甲状腺CSCs的EMT过程。
Objective:To investigate the role of 1 ,25 dihydroxyvitamin D3 (calcitriol)in the prolifera-tion and epithelial-mesenchymal transition (EMT)of cancer stem cells (CSCs)derived from anaplastic thy-roid carcinoma.Methods:Human anaplastic thyroid cancer cell line HTh74 and its doxorubicin-resistant cell line were chosen as cell models and cell viability assay was used to evaluate the cellular proliferation. Sphere formation assay was utilized to explore the effect of calcitriol on the growth of CSCs.Quantitative re-al-time PCR was used to compare the mRNA expression of EMT related genes in thyroid cancer stem-like cells with or without calcitriol treatment.Results:Calcitriol inhibited the proliferation of wild type HTh74 and its doxorubicin-resistant cell line,and the anti-proliferation effect was more pronounced in the resistant cell line.Furthermore,calcitriol inhibited the growth of CSCs derived from HTh74,down-regulated the mRNA expression of N-cadherin and Slug,which are EMT related genes(P〈0.05).Conclusion:Calcitri-ol inhibited the proliferation and EMT of thyroid CSCs.
出处
《江苏大学学报(医学版)》
CAS
2016年第5期375-379,共5页
Journal of Jiangsu University:Medicine Edition
基金
江苏省自然科学基金资助项目(BK20150476)
江苏省2014年双创人才"海外名校博士"计划
镇江市社会发展项目(FZ2014031)