摘要
目的:研究腺病毒介导的KDR启动子-单纯疱疹病毒胸苷激酶(HSV-tk)系统(AdKDR-tk)联合白细胞介素12基因对裸鼠鼻咽癌的治疗作用.方法:建立鼻咽癌裸鼠模型,将36只成瘤鼠随机分成IL-12基因组、AdKDR-tk/GCV组、IL-12基因+AdKDR-TK/GCV组和生理盐水/GCV组(对照组),每组9只.采用瘤内注射分别给予相对应的重组腺病毒液及生理盐水,24h后重复注射1次.次日起连续10d每天ipGCV1次,100mg/kg.治疗结束后处死裸鼠,检测肿瘤质量、组织形态学变化及肿瘤微血管密度.结果:IL-12基因组裸鼠鼻咽癌瘤体质量(1.82±0.78)g及肿瘤微血管密度(15.54±3.46)个/mm3和AdKDR-tk/GCV组[分别为(1.61±0.61)g,(10.69±4.12)个/mm3]与IL-12基因+AdKDR-TK/GCV组[分别为(1.04±0.52)g,(6.53±1.61)个/mm3]相比差异有显著性(P<0.05);IL-12基因组,AdKDR-tk/GCV组及IL-12基因+AdKDR-TK/GCV组与生理盐水/GCV组[分别为(2.52±1.18)g,(22.78±5.12)个/mm3]比较也存在显著差异(P<0.05).结论:HSV-TK基因和IL-12基因治疗可抑制裸鼠鼻咽癌皮下移植瘤的生长,提高机体的抗肿瘤免疫应答,两者联合运用可产生协同效应,为鼻咽癌的治疗提供新的方法.
AIM： To investigate the therapeutic efficacy of adenovirus-mediated herpes simplex virus thymidine kinase （HSV-tk） gene transfer under the driving of KDR promoter （AdKDR-tk） combined with interleukin-12（IL-12） gene against of human nasopharyngeal carcinoma（ NPC ） in nude mice. METHODS ： CNE-2 cell line was implanted subcutaneously into 36 nude mice, which were divided into 4 groups （ n = 9 each group ） ： IL-12 gene group, AdKDR-tk/GCV group, AdKDR-TK/GCV ＋ IL-12 group and saline/GCV group. Selective intratumoral injection of recombinant adenovirus or saline was then given, which was repeated 24 h later. From the following day on, 10 d GCV was given at a dose of 100 mg/（kg · d）, ip. All the treated animals were killed and the tumor weight, the histopathological changes and the microvessel density of tumors were evaluated at the end of treatment. RESULTS： The tumor weight and microvessel density in IL-12 gene group, AdKDR-tk/GCV group, AdKDR-TK/GCV ＋ IL-12 group and saline/GCV group were respectively （ 1.82 ± 0.78 ） g and （15.54 ±3.46）/mm^3; （1.61 ±0.61）g and （10.69± 4.12）/mm^3; （1.04±0.52）g and （6.53± 1.61）/mm^3; and （2. 52 ± 1. 18） g and （22. 78 ± 5. 12）/ram3. Growth and mierovessel density of NPC were significantly inhibited in IL-12 gene group and AdKDR-tk/GCV group and AdKDR-TK/GCV ＋ IL- 12 group, compared with those in saline/GCV group （P 〈 0.05 ）. Significantly better antitumor effect was observed in IL-12 gene group, AdKDR-tk/GCV group and AdKDR-TK/GCV ＋ IL-12 group, compared with that in saline/GCV group （P 〈 0.05 ）. CONCLUSION： Both HSV-tk and IL-12 inhibit the growth of nasopharyngeal carcinoma in nude mice grafted subcutaneously and efficiently induce the host anti-tumor immune response. Combination of HSV-tk and IL-12 have some synergistic effect in anti-tumor treatment, which may offer a new treatment approach for human NPC.
出处
《第四军医大学学报》
北大核心
2009年第16期1461-1463,共3页
Journal of the Fourth Military Medical University
基金
江西省教育厅科技资助项目(GJJ08427)
