重组腺病毒介导多重基因对喉癌的治疗研究

目的　探讨携带p5 3、B7 1和GM CSF基因的重组腺病毒 (BB 1 0 2 )对荷瘤裸鼠体内人喉癌细胞的基因治疗效果。方法　建立喉癌裸鼠模型 ,瘤内注射BB 1 0 2、Ad GFP和PBS ,观察肿瘤生长情况 ,并对肿瘤组织进行病理学和免疫组化检查。结果　经多因素析因方差分析 ,实验组与对照组肿瘤重量和瘤体积差异有统计学意义 (P <0 0 5 )。经治疗后 ,实验组肿瘤中未发现突变型 p5 3的表达 ,Ki6 7阳性表达率极低 ;光镜和透射电镜下可见肿瘤细胞凋亡。结论　BB 1 0 2可在喉癌细胞中有效表达 ,抑制其生长 ,诱导其凋亡 ,在喉癌基因治疗中具有较好的应用前景 ,可望发展成临床上的一种抗癌剂

Preclinical study of recombinant adenovirus carrying p53,B7-1,and GM-CSF in the treatment of human laryngeal squamous carcinoma

Objective To study the effect of a recombinant adenovirus carrying p53 gene, B7 1 gene and GM CSF (BB 102) on the nude mice transferred with laryngeal carcinoma. Methods Nude mice model bearing laryngocarcinoma was established using human laryngeal squamous carcinoma cell line (Hep 2). Large amounts of recombinant adenovirus (BB 102) were injected into the tumor. Changes in carcinoma treated with recombinant BB 102 adenovirus were observed under light and electron microscopes. Results The difference between experimental and control groups was statistically significant. The morphology of cells infected with BB 102 was analyzed for evidence of apoptosis by transmission electron microscopy. It has been shown that wild type P53 protein can inhibit cell growth and induce apoptosis, while B7 1 and GM CSF have no such effects. Conclusions The results showed that recombinant adenovirus BB 102 has significant efficacy in suppressing tumor cell growth and in inducing their apoptosis, suggesting that BB 102 might be developed into a therapeutic agent in clinical therapy of laryngeal carcinoma