腺病毒介导胞嘧啶脱氨酶基因联合αIFN治疗肾癌的实验观察.DOCVIP

临床医学论文-腺病毒介导胞嘧啶脱氨酶基因联合αIFN治疗肾癌的实验观察 【摘要】? 目的: 探讨腺病毒介导的胞嘧啶脱氨酶(CD)自杀基因联合αIFN对肾癌的治疗作用. 方法: 含CD基因重组腺病毒感染人肾癌细胞株7860，用噻唑蓝(MTT)方法观察加用5氟胞嘧啶（5Fc）或联用αIFN后的杀伤效应.建立7860裸鼠皮下移植瘤模型，瘤内注射腺病毒，腹腔注射5Fc(500 mg/kg)，联合应用αIFN时行瘤内注射，观察肿瘤生长情况. 结果: 在对感染腺病毒的7860细胞的体外杀伤实验中，CD+5Fc组的细胞存活率为(67.40±1.27)%，αIFN组的细胞存活率为(68.65±1.45)%，CD+5Fc+αIFN组细胞存活率为(34.67±2.38)%,(P=0.000)，两者之间有协同效应. 在7860裸鼠移植瘤模型中，CD+5Fc联合αIFN能够显著抑制肿瘤的生长. 结论: 腺病毒为载体的自杀基因CD加前体药5Fc联合αIFN可以明显增强抗肾癌效果. 【关键词】? 腺病毒科；遗传载体；基因疗法；胞嘧啶脱氨酶；基因；干扰素α；腺癌，透明细胞；肾肿瘤 　　【Abstract】 AIM: To study the cytotoxic efficacy of recombined treatment of human renal clear carcinoma with adenovirus mediated cytosinediaminase (CD) gene and 2IFN. METHODS: Adenovirus containing suicide gene CD was used to infect human renal clear carcinoma cells 7860, and in vitro cytotoxicity of infected 7860 cells treated by 5Fc or/and αIFN were evaluated with MTT method. The tumor growth suppression test was performed with nude mice model bearing 7860 subcutaneously injected intratumorally with AdCD combined with 5Fc (400 mg/kg) and αIFN (105 u/L). RESULTS: The rate of cell survival was only (34.67±2.38)% in the CD+5Fc+αIFN group, but (67.40±1.27)% in the CD+5Fc group and (68.65±1.45)% in the αIFN group(P=0.000). 5Fc and αIFN had obvious synergic effects. AdCD combined with 5Fc and αIFN significantly suppressed the growth of tumor in nude mice model. CONCLUSION: Recombinant adenovirus combined with prodrug and αIFN has a significant efficacy in treatment of human renal clear carcinoma. 　　【Keywords】 adenoviridae; genetic vectors; gene therapy; cytosine deaminase; genes; interferonalpha; adenocarcinoma, clear cell; kidney neoplasms 　　0? 引言??? 　　肾癌的国外发病率呈上升趋势，每年死于肾癌者近万例［1］ ，在我国也有逐年增加趋势. 早期无转移性肾癌，根治性手术是首选方案，但术后仍有复发和转移的可能，大约40%～70%的患者术后会出现肿瘤远处转移［2］. 晚期肾癌对放疗及化疗均不敏感,自杀基因及细胞因子治疗作为晚期肾癌的一种治疗方法，在肾癌的综合治疗中发挥了重要作用. 大肠杆菌胞嘧啶脱胺酶（E.coli.cytosine deaminase,CD）基因/5氟胞嘧啶（5Fc）治疗系统是单纯疱疹病毒胸苷激酶（herpes simplex virusthymidine kinase,HSVTK）基因/无环鸟苷(GCV)系统后受广泛关注的新的自杀基因