TK/GCV、CD/5-Fc双自杀基因系统治疗人结肠癌的动物实验研究

Gene therapy on nude mice models of human colocarcinoma with the system of TK/GCV and CD/5-Fc

目的:观察胸苷激酶/丙氧鸟苷(thymidine kinase/ganciclovior,TK/GCV)、胞嘧啶脱氨酶/5-氟胞嘧啶(cytosine deaminase/5-fluorocytosine,CD/5-Fc)双自杀基因系统对人结肠癌的治疗效果。方法:采用培养细胞移植法,将人结肠癌细胞系SW480接种于裸鼠背部皮下,建立裸鼠人结肠癌移植瘤模型,将32只裸鼠随机分为4组:对照组、TK/GCV组、CD/5-Fc组、TK-CD联合治疗组,每组8只,TK-CD采用逆转录病毒介导,采用瘤体内直接注射法,同时腹腔注射GCV、5-Fc治疗,观察各组小鼠的生存状况及肿瘤体积、瘤重、肿瘤生长抑制率、常规病理、生存期等指标,比较观察各治疗组的治疗效果及对荷瘤裸鼠存活的影响。结果:成功构建了SW480皮下移植瘤动物模型。各治疗组裸鼠人结肠癌移植瘤的生长均受到显著抑制,裸鼠存活期显著延长,联合基因治疗组效果更好,TK/GCV与CD/5-Fc有交互协同作用。结论:TK/GCV与CD/5-Fc对人结肠癌SW480细胞有明显抑制作用,TK/GCV、CD/5-Fc双自杀基因系统效果更强。

Objective： To investigate the effect of gene therapy on colocarcinoma with the system of TK/GCV （Thymidine kinase/Ganciclovior） and CD/5-Fc（Cytosine deaminase/5-Fluorocytosine）. Methods： With the method of transplantation of cultivated cells, 32 nude mice were injected subeutaneouly on the back with human colocarcinoma cell line SW480. They were divided into 4 groups at random, control, TK/GCV, CD/5-Fc and system of TK/GCV and CD/5- Fc group. Each group had 8 nude mice. TK, CD mediated by the reverse transcription virus were injected directly into the tumor. The common statuses of mice, the bulk, weight, inhibition rate, pathology and survival period of the tumor were detected. Results： Animal model of SW480 was successfully constructed. Each treatment group, especially the combined gene therapy group obviously inhibited the tumor＇s growth and prolonged the survival period. The difference was significant between control and treatment groups, and the combined gene therapy group worked more markedly. There was mutual effect between TK/GCV and CD/5-Fc.Conclusions： TK/GCV or CD/5-Fc obviously inhibits the growth of human colocarcinoma cell line SW480, and their combination has a greater anticancer effect.