Survivin启动子驱动腺病毒介导LRIG1基因治疗前列腺癌的体外实验  

Experimental study in vitro on gene therapy for prostate cancer with recombinant adenoviral vector carrying LRIG1 gene driven by survivin promoter

作　　者：潘东亮[1] 张录芳[2] 晋连超[1] 杨冰[1] 张祥华[1] 那彦群[1] 

机构地区：[1]北京大学首钢医院吴阶平泌尿外科医学中心,北京100144 [2]潍坊市人民医院泌尿外科,山东潍坊261041

出　　处：《现代泌尿外科杂志》2012年第5期443-445,共3页Journal of Modern Urology

基　　金：中国科学院环境化学与生态毒理学国家重点实验室开放基金(KF2011-12)

摘　　要：目的由于去势抵抗性前列腺癌(CRPC)缺乏有效治疗方法,因此催生了探索新治疗模式的需求,其中靶向基因治疗可能是治疗CRPC的较理想模式;但是CRPC的靶向性基因治疗尚没有受到应有的关注。本课题拟研究Survivin启动子驱动的重组腺病毒Ad-Surp-LRIGl对前列腺癌细胞株的体外治疗效果。方法用Ad-Surp-LRIGl和Ad-LRIGl分别感染人前列腺癌细胞PC-3M及人前列腺上皮细胞CRL-11609RWPE-1,根据报告基因EGFR表达的不同计算病毒的细胞转染率。MTT法评估Ad-Surp-LRIGl和Ad-LRIGl对PC-3M细胞生长的抑制作用。结果当MOI=25时,Ad-Surp-LRIGl在PC-3M细胞中的转染效率为81.24%,在CRL-11609RWPE-1细胞中转染率为0,在两种细胞内的转染率比较差异有显著性意义(χ2=65.18,P=0.000);Ad-LRIGl在PC-3M细胞中的转染效率为77.22%,在CRL-11609RWPE-1细胞中转染率为71.68%,转染率比较差异无显著性意义(χ2=0.051,P=0.802)。Ad-Surp-LRIGl和Ad-LRIGl在PC-3M细胞中的转染率相比,差异无显著性意义(χ2=0.013,P=0.796)。在常规培养1d后PBS组的细胞生长速度即开始超过Ad-Surp-LRIGl组和Ad-LRIGl组细胞,4d后细胞生长速度差异显著(χ2=15.37,P=0.001),而Ad-Surp-LRIGl组和Ad-LRIGl组细胞生长速度无明显差异。结论 Ad-Surp-LRIGl能选择性转染人前列腺癌细胞PC-3M,能明显抑制体外前列腺癌细胞的生长。Objective To study the experimental therapy in vitro for prostate cancer with recombinant adenoviral vector carrying LRIG1 gene driven by survivin promoter. Methods Human prostate cancer cell line PC-3M and human prostate epithelial cells CRL-11609 RWPE-1 were infected with Ad-Surp-LRIG1 and Ad-LRIG respectively. The infection efficiency of Ad-Surp-LRIG1 and Ad-LRIG were evaluated by means of expression of EGFR. MTT method was used to test cell growth inhibition ratio of Ad-Surp-LRIG1 and Ad-LRIG1. Results When MOI= 25,the transfection efficiency of Ad-Surp-LRIGI was 81.24% in PC-3M cells and 0 in CRL-11609 RWPE-1 cells （X2; 65.18, P = 0. 000）, while the transfection efficiency of AdLRIG was 77.22% in PC-3M cells and 71.68% in CRL-11609 RWPE-1 cells （χ2 =0. 051,P=0. 802）. The transfection efficiency difference of Ad-Surp-LRIG1 and Ad-LRIG in PC-3M cells wasn＇t statistically significant （χ2 = 0. 013, P = 0. 796）. PC- 3M ceils in PBS began to grow faster than Ad-Surp-LRIGl and Ad-LRIGI group 1 day after normal culture. This difference of growth rate was significant 4 days after transfection （χ2 = 15.37, P= 0. 001）. There was no significant difference in cell growth rate of Ad-Surp-LRIG1 group and Ad-LRIG1 group. Conclusions The recombinant adenoviral vector of Ad-Surp-LRIG1 could selectively transfect human prostate cancer celt line PC-3M, which could significantly inhibit the growth of prostate cancer cells in vitro.

关 键 词：前列腺癌 腺病毒 SURVIVIN启动子 LRIG1基因 治疗 

分 类 号：R737.14[医药卫生—肿瘤]