中文摘要：

目的探讨肿瘤坏死因子相关凋亡诱导配体（TRAIL）联合衣霉素促甲状腺未分化癌细胞株凋亡的作用机制。方法通过单用TRAIL（TRAIL组）、衣霉素（衣霉素组）、联合用药组（TRAIL＋衣霉素组）对多种甲状腺未分化癌细胞株进行作用,并以正常甲状腺上皮细胞株HTori-3作对照,利用流式细胞仪分析各组细胞周期变化及各组细胞凋亡状态;采用蛋白印迹杂交法检测衣霉素处理前后各组细胞细胞周期蛋白D1蛋白表达水平;利用微小RNA干扰技术及质粒转染技术探讨细胞周期蛋白D1对依霉素增敏TRAIL效应的影响。结果 TRAIL与衣霉素单用对甲状腺癌细胞均无明显杀伤作用,最高细胞凋亡率分别为10.68%、10.14%;联合用药组细胞凋亡率最大达54.77%,与TRAIL组和衣霉素组相比,具有统计学差异（P〈0.05）。与对照组相比,衣霉素组和联合用药组细胞周期蛋白D1水平明显降低。微小RNA干扰可以特异性下调细胞周期蛋白D1进而增加ARO细胞对TRAIL的敏感性;而细胞周期蛋白D1过表达ARO细胞中细胞凋亡率降低22.7%。结论在体外单用TRAIL对甲状腺癌细胞增殖无明显抑制作用,衣霉素明显增加肿瘤细胞对TRAIL敏感性,其增敏机制至少部分与下调细胞周期蛋白D1水平有关。

英文摘要：

Objective To investigate the combined effect of recombinant human tumor necrosis factor-related apoptosis-inducing ligand（TRAIL）with tunicamycin on thyroid cancer cell.Methods Thyroid epithelial cell line HTori-3 was used as control.After being treated with TRAIL and/or tunicamycin,the cytotoxic effect in ARO cells was measured by MTT and flow cytometry assay.The expression level of cyclin D1 was detected by Western blot.Small interfering RNA and cyclin D1 plasmid were used to detect the effect of cyclin D1 on TRAILinduced apoptosis which was enhanced by tunicamycin.Results No obvious cell-killing was found in ARO cells when treated with TRAIL or tunicamycin alone.The apoptotic rate in ARO cells treated with both TRAIL and tunicamycin was significantly higher than that in the cells treated with TRAIL or tunicamycin alone（54.77% vs 10.68% or 10.14%,P〈0.05）.The expression level of cyclin D1 significantly decreased in ARO cells after combined treatment with TRAIL and tunicamycin.Down-regulated expression of cyclin D1 by small interfering RNA enhanced TRAIL-induced apoptosis,but overexpressed cyclin D1 reduced the apoptotic rate of ARO cells by 22.7%.Conclusion Tunicamycin could markedly enhance the antitumor effect of TRAIL in ARO cells by down-regulating the expression of cyclin D1.