衣霉素联合TRAIL促甲状腺癌细胞凋亡机制的研究  

Survivin-mediated sensitizing effect of tunicamycin on TRAIL in thyroid cancer cells

作　　者：都镇先[1] 张海燕[2] 邓娓娓[2] 王华芹[3] 

机构地区：[1]中国医科大学附属第一医院内分泌科,辽宁沈阳110001 [2]中国医科大学附属第一医院老年病科,辽宁沈阳110001 [3]中国医科大学基础医学院生化与分子生物教研室,辽宁沈阳110001

出　　处：《中华肿瘤防治杂志》2009年第14期1041-1044,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金(30740086);沈阳市科委支持项目(1063316-1-00)

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系凋亡的作用机制。方法:通过TRAIL单用或联合衣霉素对多种甲状腺未分化癌细胞系进行作用,并以正常甲状腺上皮细胞系HTori-3作对照,采用蛋白印迹杂交法检测衣霉素处理前后各组细胞TRAIL死亡受体,诱杀受体和凋亡相关分子的蛋白表达水平。流式细胞术检测各组细胞凋亡状态。结果:与对照组相比,衣霉素作用后,肿瘤细胞死亡受体DR4、DR5和诱杀受体DcR1、DcR2表达无明显变化(P>0.05),而存活素水平明显降低,P<0.05。TRAIL与衣霉素单用对甲状腺癌细胞均无明显杀伤作用,最高凋亡细胞比率分别为10.68%和10.14%;衣霉素与TRAIL联合组凋亡细胞比率最大达60.5%;但在存活素过表达甲状腺未分化癌ARO细胞中,凋亡细胞比率降低50%左右。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存活素水平有关。OBJECTIVE： To investigate the combined effect of recombinant human TRAIL with tunieamycin on thyroid cancer cells. METHODS： Normal thyroid epithelial cell HTori-3 was used as control. After being treated with TRAIL and tunieamyein, the cytotoxic effect in ARO cells was measured by MTT and flow eytometry assays. The expression levels of TRAIL death receptors and TRAIL decoy receptors were assayed by real time RT-PCR and Western blot analysis. RESULTS： The expression levels of death receptors DR4 and DR5, as well as decoy receptors DcR1 and DcR2 were not influenced in ARO cells treated with TRAIL and tunicamyein （P〉0.05）, while the expression of Survivin was significantly decreased, P 〈0.05. TRAIL or tunicamycin alone induced 10.68% and 10.14% apoptotic cells, respectively. The combination of TRAIL and tunicamyein caused 60.5% apoptotie cells, whereas, overexpression of Survivin in ARO reduced the combinational effects of TRAIL and tunicamycin to 50% CONCLUSION： ARO cells are resistant to TRAIL treatement, tunieamycin markedly enhanced the antitumoral effects of TRAIL in ARO cells, at least in part, via suppression of Survivin expression.

关 键 词：肿瘤坏死因子相关凋亡诱导配体 衣霉素 甲状腺肿瘤 存活素 

分 类 号：R736.1[医药卫生—肿瘤]