塞来昔布对正常脑胶质细胞和脑胶质瘤细胞放射增敏效应的比较及其机制  

Radiosensitization effects of celecoxib on glioblastoma： comparison with oligodendrocyte cell line

作　　者：聂亮琴[1] 周菊英[1] 王利利[1] 徐晓婷[1] 秦颂兵[1] 

机构地区：[1]苏州大学附属第一医院肿瘤放疗科,215006

出　　处：《中华放射医学与防护杂志》2014年第5期342-344,375,共4页Chinese Journal of Radiological Medicine and Protection

基　　金：国家自然科学基金青年科学基金（81302384）

摘　　要：目的 探讨塞来昔布对正常少突胶质细胞（oln93）及脑胶质瘤细胞（u373）的放射增敏作用及其作用机制.方法 将两种细胞按空白处理、单独接受塞来昔布或X射线、塞来昔布联合X射线4种不同处理方式分为对照组、给药组、照射组和联合组,MTT法、克隆形成法对比两种细胞的增殖和放射敏感性,流式法测细胞的周期分布,Western blot法分析相关蛋白表达.结果 与未加药物相比,塞来昔布能抑制oln93细胞和u373细胞生长（t=2.215 ～ 30.996,P＜0.05;t =0.383～11.732,P＜0.05）,但相同药物浓度下抑制两种细胞差异无统计学意义.放射增敏比SER分别为1.13和1.21,并诱导G0/G1期阻滞（t=-6.1 ～5.141,P＜0.05）.联合组与照射组比较,oln93细胞发生S期阻滞（t=-18.174,P＜0.05）,Cyclin A蛋白表达增加（t=-8.087,P＜0.05）;u373细胞发生G2/M期阻滞,Cyclin B1、DNA-PKcs、MRE11 蛋白表达下降（t=-8.838～10.45,P＜0.05）.结论 塞来昔布对u373的放射增敏作用比oln93细胞明显,其机制与调节细胞周期分布及DNA损伤修复有关.Objective To compare the radiosensitivity effect of celecoxib on oln93 and u373 cells,and to explore the related mechanism.Methods Both oln93 cells and u373 cells were respectively divided into control group,drug group,radiation group and combined group when treated with celecoxib and irradiation.Cell survival ratio was evaluated by MTT assay and clogenic assay.Flow cytometry and Western blot assay were used to measure cell cycle and protein expression.Results Celecoxib had a similar effect on oln93 and u373 cells in enhancing the radiosensitivity （t =2.215-30.996,P ＜ 0.05 ; t =0.383-11.732,P＜0.05）and blocking cellcycle in G0/G1（t=-6.1-5.141,P＜0.05）.Compared with the radiation group,the combined group showed S phase arrest（t =-18.174,P ＜ 0.05）,and increase of Cyclin A protein （t =-8.087,P ＜ 0.05） in oln93 cells,and G2/M arrest and decrease of Cyclin B1 and DNA-PKcs and MRE11 protein （t =-8.838-10.45,P ＜ 0.05） in u373 cells.Conclusions Celecoxib illustrates a more sensitive radiosensitivity to u373 cells by regulating its cell cycle and DNA damage repair.

关 键 词：COX-2抑制剂 塞来昔布 放射增敏 脑胶质瘤细胞 

分 类 号：R14[医药卫生—公共卫生与预防医学]