PRDX1在蛋白酶体抑制剂诱导人甲状腺癌细胞凋亡中的作用  

The role of PRDX1 in apoptosis of thyroid cancer cells mediated by proteasome inhibitor

作　　者：郭佳[1] 孟欣[2] 都镇先[1] 王华芹[2] 张海燕[1] 

机构地区：[1]中国医科大学附属第一医院,辽宁沈阳110001 [2]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：《现代肿瘤医学》2015年第4期440-444,共5页Journal of Modern Oncology

基　　金：国家自然基金资助项目(编号:81301838);沈阳市科技厅资助项目(编号:F13-220-9-44)

摘　　要：目的:探讨过氧化还原蛋白(Peroxiredoxin1,PRDX1)在蛋白酶体抑制剂诱导人甲状腺癌细胞凋亡中的作用。方法:选取人甲状腺癌细胞,设立对照组和蛋白酶体抑制剂处理组;实时定量PCR法、蛋白印迹法检测PRDX1在各组甲状腺癌细胞中的表达;微小RNA干扰技术、过表达PRDX1质粒转染细胞;应用流式细胞仪检测细胞凋亡。结果:与对照组相比,MG132处理组中PRDX1 mRNA及蛋白表达水平显著增加(P<0.01);蛋白酶体抑制剂组、siPRDX1组PRDX1 mRNA及蛋白显著低于随机序列组及空白组(P<0.05);siPRDX1转染细胞组中细胞凋亡率显著高于随机序列组及空白组(P<0.05);在8305C和8505C细胞中也得到相似的结果;siPRDX1+PRDX1表达载体组对MG132介导的凋亡无显著影响(P>0.05)。结论:siPRDX1增加蛋白酶体抑制剂对未分化甲状腺癌细胞的凋亡作用,而这种作用可以被外源性PRDX1所抑制。Objective ：To investigate the role of Peroxiredoxins （PRDX1） in apoptosis of thyroid cancer cells af- fected by proteasome inhibitor. Methods：A panel of cancer cells were selected for the investigation, set up control group and proteasome inhibitor treatment groups. The expression of PRDXI mRNA and protein in each group of thy- roid cancer cells was confirmed by real - time RT - PCR and Western blot. The small interfering RNA （siRNA） and/ or construction of PRDX1 plasmid was transfected thyroid cancer cells. Flow cytometry was used to measure apoptotic cells. Results：MG132 significantly elevated PRDX1 mRNA and protein levels when compared with control group （P 〈 0.01 ）. siPRDX1 significantly suppressed MG 13 2 - mediated upregulation of PRDX 1 mRNA, protein levels （P 〈 0. 05 ）, siPRDX1 increased the sensitivity of FRO cells to proteasome inhibitors when compared with parental and scramble groups （P 〉 0. 05 ）. Similar to FRO cell, siPRDX1 also increased the sensitivity of 8305C and 8505C cells to MG132（P 〈 0. 05 ）. Overexpression of PRDX1 recovered the responsiveness of siPRDX1 to MG132 -induced cell death. Condusion：siPRDX1 enhances the death of undifferentiated thyroid cancer cells, which can be inhibited by the exogenous PRDX1.

关 键 词：蛋白酶体抑制剂 微小RNA干扰 过氧化还原蛋白1 甲状腺癌 

分 类 号：R73-36[医药卫生—肿瘤] R736.1[医药卫生—临床医学]