TK/GCV、CD/5-Fc双自杀基因系统治疗结肠癌的实验研究

Treatment of human colocarcinoma with gene therapy system of TK/GCV and CD/5-Fc in nude mice

目的观察胸苷激酶/丙氧鸟苷(TK/GCV)、胞嘧啶脱氨酶/5-氟胞嘧啶(CD/5-Fc)双自杀基因系统对结肠癌的治疗效果,并结合研究结果进行作用机理的分析。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:空白对照组,TK/GCV治疗组,CD/5-Fc治疗组,TK/GCV+CD/5-Fc联合治疗组,每组8只。TK/GCV+CD/5-Fc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。结果各治疗组裸鼠人结肠癌移植瘤的生长均受到显著抑制,治疗后各组体积数增加(P<0.05),治疗组裸鼠存活期显著延长,TK/GCV+CD/5-Fc联合治疗组效果最好,疗效q值=1.675>1.15,即TK/GCV、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 curative effect of the system of TK/GCV and CD/5-Fc on colocarcinoma and analyze the corresponding mechanism. Methods By using transplantation of the cultivated cells, human colocarcinoma cell line SW480 was injected subcutaneously on the back of nude mice to establish the animal model of human colocarcinoma. Thirty-two nude mice were divided randomly and equally into four groups, ie, control group, TK/GCV group （group TK）, CD/5-Fc group （group CD） and group of system of TK/GCV and CD/5-Fc （group TK-CD）. TK-CD mediated by the reverse transcription virus was injected directly into the tumor. At the same time, the nude mice were given intraperitoneal injection of GCV and 5-Fc nude for observing parameters including common status, tumor bulk, tumor weight, inhibition rate of tumor growth, pathology and survival period of mice and comparing treatment effect and survival rate in each group. Results Tumor growth was obviously inhibited in each treatment group, especially in group of system of TK/GCV and CD/5-Fc, with tumor bulk in control group, group TK, group CD and group TK-CD for （2. 618±0. 223） cm^3 , （2. 156±0. 242） cm^3 , （2. 044±0. 191） cm^3 and （1. 052±0. 173） cm^3 respectively （ P 〈0. 05）. The survival period was significantly prolonged to （54. 3 ± 6. 5） days, （68.7±6.0） days, （69.7±3.5） days and （79.3±4.7） days in control group, group TK, group CD and group TK-CD respectively （ P 〈0.05）. There was mutual effect between TK/GCV and CD/5-Fc （ q = 1. 675〉1.15）. Conclusion TK/GCV and CD/5-Fc can obviously inhibit the growth of human colocarcinoma cell line SW480 and the combined genes exert greater antitumoral effect.