重组人p53腺病毒注射液联合泰索帝对人肺腺癌细胞生长的抑制作用  

EFFECT OF RECOMBINANT ADENOVIRUS-p53 COMBINED WITH DOCETAXEL ON THE GROWTH INHIBITION OF HUMAN LUNG ADENOCARCINOMA CELL LINES

作　　者：王朝霞[1] 王科明[1] 韩亮[2] 陆彬彬[3] 束永前[3] 

机构地区：[1]南京医科大学第二附属医院肿瘤科,江苏南京210011 [2]江苏徐州市第四人民医院肿瘤科,江苏徐州221009 [3]南京医科大学第一附属医院肿瘤中心,江苏南京210029

出　　处：《实用临床医药杂志》2006年第6期13-17,共5页Journal of Clinical Medicine in Practice

基　　金：江苏省卫生厅医学科技发展项目(H200211)

摘　　要：目的探讨基因治疗药物重组人p53腺病毒注射液（Aap53）联合化疗药物泰索帝（多西紫杉阵，Docetaxel）对人肺腙癌GLC-82（含突变型p53基因）及A549（含野生型p53基因）细胞的增殖抑制、凋亡诱导作用。方法将重组腺病毒载体所携带的野生型p53牡凼导人人肺腺癌细胞株GLC82及A549。并联合应用化疗药物多西紫杉醇，通过Western blot法分析外源野生型p53基因在细胞内的表达，MTT法和流式细胞术观察对细胞生长抑制及细胞周期、凋亡的影响。结果通过Western blot让实了外源p53基因能在GLC-82及A549细胞中高效表达。MTT法观察到Ad—p53对肺癌细胞的抑制作用量时间依赖性．剂量依赖性效应，100MOI的Ad—p53与Doeetaxel 5mg/L联合应用后72h。对A549细胞生长的抑制率达（5196±076）％，单用的抑制率分别为（23．44±0．54）％、（40．53±1．37）％；对GLC-82细胞生长的抑制率达（6242±1．43）％，单用的抑制率分别为（41．51±0．59）％、（48．39±0．88）％。流式细胞术检测结果显示，Ad-p53与Docetaxel联合应用能使细胞阻滞于G0-G1期，S期细胞比例明显减少，引起的A549细胞凋亡率为（23．35±0．64）％，单用的凋亡率分别为（15．35±131）％、（093±035）％；GLC-82细胞凋亡率为（47．73±1．17）％，单用的凋亡率分别为（20．88±0.71）％．（1．16±0．52）％。结论Ad—p53与化疗药物Docetaxel联用能照著协同抑制肺腺癌细胞的生长，增加化疗敏感性。Objective To evaluate the effects of recombinant adenovirus-p53 （Gendicine） combined with docetaxel on the growth inhibition of human lungadenocarcinoma cell lines. Methods Human lung adenocarcinomacell lines GLC-82 （including mutant p53） and A549 （including wild- type p53） were treated with Ad-p53, docetaxel or Ad-p53 ＋ docetaxel respectively, p53 expression was detected by Western blot, The cell growth inhibition and cell cycle apoptosis were assessed with MTT and flow cytometry. Results High-level p53 expression was detected in Ad-p53 infected GLC-82 and A549 cells by Western blot. There was a dose-dependent and time-dependent inhibition of cell proliferation by Ad - p 5 3. After combining treatment with Ad - p 5 3 （ 1 0 0 MOI ） and docetaxel （5 rag/l_.） for 72 hours, the growth inhibition rate of A549 cells was （51.96 ± 0.76） %, which was significantly higher than that in Ad-p53 group （23.44 ± 0.54） % and docetaxel group （40.53 ± 1.37） % ; and the growth inhibition rate of GLC-82 cells was （62.42 ± 1.43） %, which was significantly higher than that in Ad-p53 group （41.51 ± 0.59） % and docetaxel group （48.39 ± 0. 88） %. Combined administration of Ad-p53 and docetaxel remarkably arrested A549 and GLC-82 cells in G0-G1, and cells in Sphase significantly decreased. Meanwhile the apoptotic rate of A549 cells was （23.35 ± 0.64） % in Ad-p53 ＋ doeetaxel group, which was significantly higher than that in A＆p53 group （15.35 ± 1.31） % and docetaxel group（0.93 ± 0.35） %. The almptotic rate of GLC-82 cells was（47.73 ± 1.17） % in Ad-p53 ＋ doeetaxel group, which was significantly higher than that in Ad-p53 group （20.88 ± 0.71） % and docetaxel group （1.16 ± 0.52） %. Conelusion Ad-p53 （Gendicine） combined with docetaxel shows significantly synergistic inhibition effects on the growth of human lung adenocarcinoma cell lines.

关 键 词：肿肿瘤 基因治疗 P53基因 多西紫杉醇 

分 类 号：R734.2[医药卫生—肿瘤]