WTp53基因联合TK／GCV、CD／5-FC系统抑制结肠癌肝转移的实验研究

Inhibitory effects of WTp53 gene in combination with TK/GCV and CD/5-FC systems on liver metastasis of colon carcinoma in nude mice

目的研究WTp53基因联合TK／GCV、CD／5-FC系统对结肠癌肝转移的抑制作用。方法32只裸鼠随机分为4组，每组8只。脾内注射法建立结肠癌肝转移动物模型。第1组：脾内注射SW480细胞（对照组）；第2组：脾内注射SW480／p53细胞；第3组：脾内注射SW480／TK-CD细胞，腹腔注射GCV、5-FC；第4组：脾内注射SW480／p53与SW480／TK-CD等比例混合细胞，腹腔注射GCV、5-FC。观察各组裸小鼠的肝转移率、肝转移瘤数目、肿瘤细胞凋亡指数（AI）、生存期等指标。结果各治疗组裸鼠肝转移的发生率下降，平均肝转移瘤数减少，其动物的生存期延长，肝转移瘤内的癌细胞凋亡率增高。联合基因治疗组效果最好，且WTp53与TK／GCV、CD／5-FC有交互协同作用。结论WTp53基因与TK／GCV、CD／5-FC系统联合应用具有协同效应，可有效地抑制结肠癌肝转移的形成。

Objective To investigate the inhibitory effects of WTp53 gene in combination with TK/GCV and CD/5-FC systems on liver metastasis of colon carcinoma. Methods Thirty-two nude mice were randomized into 4 groups with 8 in each. The model of liver metastasis of colon carcinoma was established by spleen injection. In group A, the mice were injected with SW480 alone into the spleen. The animals in group B were injected with SW480/p53 cells into the spleen. In group C, the mice were injected with SW480/TK-CD cells into the spleen and intraperitoneal injection of GCV and 5-FC. The mice in group D were injected with SW480/p53 and SW480/TK CD into the spleen. Liver metastatic rate, number of liver metastasis, tumor cell apoptotic index and life span and other indexes of nude mice in the 4 groups were determined and compared. Results The metastatic rate of colon carcinoma was lower in groups B, C and D than in group A. The average number of liver metastasis decreased, life span of nude mice prolonged and the apoptotic index of cancer cells in the liver metastasis increased in groups B, C and D than in group A. The combined genes in group D worked the best and there was mutual effect between WTp53 and the combination of TK/GCV and CD/5-FC. Conclusions Synergistic effect is acquired by combining WTp53 gene with TK/GCV and CD-5-FC systems. This combination can efficiently inhibit the formation of liver metastasis of colon carcinoma.