pcDNA3.1-Egr.1p-p16基因联合放射治疗对裸鼠肿瘤的作用  

Anti-tumor effect of pcDNA3.1-Egr.1p-p16 gene combined with radiotherapy in tumor-bearing nude mice

作　　者：马红兵[1] 王西京[1] 胡海涛[2] 狄政莉[1] 夏辉[3] 王铮[3] 李琤[3] 韩志楷[3] 马洁[3] 吴丛梅[4] 

机构地区：[1]西安交通大学第二医院肿瘤科,西安710004 [2]西安交通大学医学院解剖教研室,西安710068 [3]中国医学科学院肿瘤研究所分子肿瘤学国家重点实验室,北京100021 [4]汕头大学医学院生物教研室,汕头515031

出　　处：《中南大学学报（医学版）》2005年第1期7-10,15,共5页Journal of Central South University ：Medical Science

基　　金：陕西省科技攻关基金(2002K10 G3);西安交通大学第二医院科研基金(2001YJ 04

摘　　要：目的:探讨pcDNA3.1 Egr.1p p16基因联合放射治疗移植人胰腺癌细胞JF 305裸鼠的抗肿瘤作用的 适宜照射剂量和质粒注入量。方法:不同剂量X射线照射(2,10,20Gy)及瘤内不同量脂质体包裹的pcDNA3.1 Egr.1p p16质粒(10,20,30μg)注入接种JF305胰腺癌细胞的裸鼠体内,测定各组裸鼠体积以观察各种处理抑瘤效 应的差异,并用RT PCR检测放射治疗后48h各组肿瘤局部p16mRNA水平。结果:质粒注入后接受20GyX射线 照射组照射后4～28d,肿瘤生长速率明显低于2Gy和10Gy照射组(P<0.05)。质粒注入量为20μg或30μg的 联合治疗组照射后4～28d,肿瘤生长速率明显低于注入量为10μg的联合治疗组(P<0.05)。单纯接种 pcDNA3.1 Egr.1p p16质粒组和接种pcDNA3.1 Egr.1p p16质粒照射组小鼠的肿瘤组织内有p16mRNA表达,且 pcDNA3.1 Egr.1p p16质粒照射组的p16mRNA水平明显高于单纯pcDNA3.1 Egr.1p p16质粒组(P<0.05)。结 论:pcDNA3.1 Egr.1p p16基因联合放射治疗小鼠体内抗肿瘤作用的适宜射线照射剂量为20Gy,质粒注入量为20 μg;pcDNA3.1 Egr.1p p16基因联合放射治疗的抗肿瘤作用明显优于单纯放射治疗或单纯基因治疗,这可能与辐射 激活Egr.1p基因后增强抑瘤基因p16的表达有关。Objective To investigate the optimal doses of X-ray irradiation and plasmid injection in the anti-tumor effect of the pcDNA3.1-Egr.1p-p16 gene combined with radiotherapy in vivo. Methods We observed the anti-tumor effect of the pcDNA3.1-Egr.1p-p16 gene combined with radiotherapy with different doses of X-ray irradiation (2, 10, 20Gy) and plasmid injection (10, 20, 30μg) in nude mice with JF-305 pancreatic carcinoma, and detected the expression of p16 in tumor by RT-PCR. Results The tumor growth rate of the nude mice irradiated locally with 20Gy X-rays after the plasmid injection was significantly lower (P<0.05) than that of the nude mice irradiated locally with 2Gy or 10Gy X-ray 3 days after the irradiation. The tumor growth rate of the nude mice injected locally with 20μg or 30μg plasmid was significantly lower (P<0.05) than that of the nude mice injected locally with 10μg plasmid. Both pcDNA3.1-Egr.1p-p16 group and pcDNA3.1-Egr.1p-p16 +20 Gy group had p16 mRNA expression,but the mRNA level of pcDNA3.1-Egr.1p-p16 +20 Gy group was higher than that of pcDNA3.1-Egr.1p-p16 group. Conclusion In the pcDNA3.1-Egr.1p-p16 gene combined with radiotherapy in vivo the optimal dose of X-ray irradiation was 20Gy and the optimal dose of plasmid injection was 20μg. The anti-tumor effect of pcDNA3.1-Egr.1p-p16 combined with radiotherapy is better than that of radiotherapy or gene therapy alone, which may be related with the enhanced p16 expression in tumor after the irradiation.

关 键 词：pcDNA3.1-Egr.1p-p16重组质粒 基因联合放射治疗 X射线 抗肿瘤作用 剂量 质粒注入量 

分 类 号：R735.9[医药卫生—肿瘤]