WTp53基因联合TK/GCV、CD/5-Fc系统治疗人结肠癌的实验研究

Gene therapy with wild type p53 gene and the system of TK/GCV and CD/5-Fc on the nude mice models of humancolocarcinoma

目的:观察WTp53基因联合TK/GCV、CD/5-Fc系统对人结肠癌的治疗效果,并探讨其作用机理。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、WTp53组、TK、CD组、WTp53与TK、CD组,每组8只,WTp53采用脂质体介导,TK、CD采用逆转录病毒介导。将WTp53、TK、CD注入移植瘤体内,瘤内注射TK、CD的裸鼠同时腹腔注射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: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,WTp53、与TK、CD有交互协同作用。结论:WTp53、TK/GCV、CD/5-Fc对人结肠癌SW480细胞有明显抑制作用,WTp53基因联合TK/GCV、CD/5-Fc系统效果更强。

Objective ： To investiaate the effect of the 8ene therapy with WTp53 8ene and the system of TK/GCV and CD/5-Fc on colocarcinama and to explore how the 8enes work. Methods ：The transplantation of cultivated cells was adopted. Nude mice were injected subcutaneously on the back with human colocarcinma cell line SW480, so as to establish the animal model of human colocarcinama. 32 nude mice were divided into 4 8roups at random, which were control 8roup,the 8roup of WTp53, the 8roup of the system of TK/GCV and CD/5-Fc and the 8roup of WTp53 and the System of TK/GCV and CD/5-Fc,and each 8roup had 8 nude mice. WTp53 mediated by Lipofectamine and TK,CD mediated by the reverse transcription virus were injected directly into the tumor. Nude mice common status,tumor＇s bulk,tumor＇s weiaht , inhibition rate of tumor＇ s 8rowth, pathotoay, survival period, etc, were investiaated. Results ： Eachtreated group especially the combined gene therapy group obviously inhibited the tumor＇s growth and prolonged the survival period significantly. The difference was significant between control group and treated groups,and the combined gene therapy group worked more markedly. There was mutual effect between the group of WTp53 and the group of the system of TK/C-CV and CD/5-Fc. ConelusJon ：WTp53 ,TK/GCV,or CD/5-FC obviously inhibits the growth of human colocarcinama cell line SW480, however, the combined genes therapy may have a greater antitumoral effect.