放射诱导正反馈基因环路调控Wt-p53表达对肺腺癌移植瘤的抑制作用  

Inhibitory effects of wt-p53 regulated by radioinducible positive feedback genetic circuit on transplanted lung adenocarcinoma in nude mice

作　　者：毛丽伟[1] 王卫东 廖国清[1] 王红梅[1] 陈正堂 

机构地区：[1]解放军309医院肿瘤科,北京100091 [2]第三军医新桥医院全军肿瘤诊治研究所,重庆400037

出　　处：《免疫学杂志》2010年第6期473-476,共4页Immunological Journal

摘　　要：目的:探讨放射控导的wt-p53蛋白正反馈基因环路对肺腺癌细胞裸鼠移植瘤放射增敏作用及机制。方法:将治疗组pE6R4-p53-EGFP/H1299细胞和对照组pE6-p53-EGFP/H1299、pR4-p53-EGFP/H1299、H1299(p53-/-)细胞分别注射于裸鼠背部皮下,建立裸鼠移植瘤模型;X线照射后,绘制肿瘤生长曲线;计算各组抑瘤率;免疫组化法检测瘤组织wt-p53表达;计算TCD50及放射增敏比(SER)。结果:pE6R4-p53-EGFP/H1299+IR组移植瘤生长明显受抑制,抑瘤率(86.41%)明显高于对照组pE6-p53-EGFP/H1299+IR组(70.76%)、pR4-p53-EGFP/H1299+IR组(35.53%)和H1299+IR组(12.58%)。免疫组化提示pE6R4-p53-EGFP/H1299组比pR4-p53-EGFP/H1299、pE6-p53-EGFP/H1299组wt-p53蛋白表达量明显增高。pE6R4-p53-EGFP/H1299组和对照组pE6-p53-EGFP/H1299和H1299(p53-/-)荷瘤鼠TCD50分别为12.1Gy、15.2Gy和19.4Gy,SER分别为1.6和1.28。结论:放射控导的wt-p53蛋白正反馈基因环路能在体内正常激活并发挥抗肿瘤生物学效应,且显著增加了瘤组织对放射的敏感性。We aimed to investigate the radio-sensitivity enhancement and its mechanism of artificial wt-p53 positive feedback circuit guided by irradiation on the transplanted lung adenocarcinoma in nude mouse. Nude mouse lung adenocarcinoma transplant model was established by Subcutaneous injection of pE6R4-p53-EGFP/H1299, pE6-p53-EGFP/H1299, pR4-p53-EGFP/H1299, and H1299 （p53^-/-） cells, respectively. Tumor size in these nude mice was measured at the indicated time points post exposure to irradiation, and tumor growth curve was obtained. The morphology of the tumors was observed by HE staining and the expression of wt-p53 protein was detected by immunohistochemistry assay. TCD50 and SER value were calculated. The growth curves of xenograft tumors show that the tumor inhibition ratio in pE6R4-p53-EGFP/H1299/IR group （86.41%） was higher than that in pE6-p53-EGFP/H1299＋ IR group （70.76%）, pR4-p53-EG FP/H1299＋IR group （35.53%） and H1299＋IR group （12.58%）. Positive wt-p53 staining was increased greatly in pE6R4-p53-EGFP/H1299 group compared with other control groups. The TCD50 values were 12.1 Gy, 15.2 Gy and 19.4 Gy in pE6R4-p53-EGFP/H1299, pE6-p53-EGFP/H1299 and H1299 （p53^-/-） group, respectively. The SER of pE6R4-p53- EGFP/H1299, pE6-p53-EGFP/H1299 was 1.6 and 1.28, respectively. The results suggest that irradiation-induced wt-p53 positive feedback circuit can induce anti-tumor effect and enhance the radio-sensitivity of the transplanted lung adenocarcinoma in nude mouse.

关 键 词：基因环路 X线 肺腺癌 

分 类 号：R734.2[医药卫生—肿瘤]