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目的探讨组织特异性胞嘧啶脱氨酶/5-氟胞嘧啶(CD/5-FC)系统热化疗对裸鼠结肠癌肝转移的靶向治疗效果。方法脂质体法转CD基因至人结肠癌LoVo细胞株。45只BALB/c裸鼠采用经门静脉注射转CD基因LoVo细胞(LoVo-CEACD,0.2mL,107/L)至裸鼠体内建立模型后,随机分为3组,每组15只,即对照组、前药治疗组及前药热疗组。3组分别经腹腔注射42℃生理盐水和38℃5-FC及42℃5-FC,5-FC剂量为500mg/(kg.d),连续21d后,待动物自然死亡,观察自然生存期、肝脏转移率、肝脏转移结节数;切取肝脏转移瘤组织,正常肝组织及胃、肺、胰腺、小肠、大肠组织,行RT-PCR检测各组织CD基因表达,观察各组织病理学变化、肿瘤细胞凋亡指数。结果目的基因在肝脏转移瘤组织中能有效表达,在正常肝组织及胃、肺、胰腺、小肠、大肠组织中无表达。3组的自然生存期分别为(25.80±3.65),(34.27±4.08),(41.87±3.91)d;肝脏转移率分别为100.0%(15/15),40.0%(6/15),13.3%(2/15);平均肝脏转移结节数分别为(2.93±1.16),(0.80±1.01),(0.20±0.56)个。前药治疗组和前药热疗组的自然生存率明显长于对照组(P<0.05);3组间的肝脏转移率两两比较,差异均有统计学意义(均P<0.05),肿瘤细胞凋亡指数(AI)分别为4.59%,9.87%,17.4%,各组比较,差异均有统计学意义(P<0.05)。结论组织特异性CD/5-FC系统热化疗对裸鼠结肠癌肝转移有明显的靶向抑制作用。
Objective To investigate the therapeutic effect of tissue-specific cytosine deaminase / 5-fluorocytosine (CD / 5-FC) system on liver metastases of colon cancer in nude mice. Methods The CD gene was transfected into human colon cancer LoVo cell line by liposome method. Forty five BALB / c nude mice were injected into LoVo cells (LoVo-CEACD, 0.2 mL, 107 / L) by intravenous injection into nude mice and then divided into 3 groups randomly, 15 in each group , Prodrug treatment group and prodrug hyperthermia group. The animals were sacrificed at 42 ℃, 38 ℃ 5-FC and 42 ℃ 5-FC by intraperitoneal injection at 500mg / (kg · d) for 5 days. After 21 days of continuous operation, the animals were sacrificed and their natural life was observed. Liver metastasis and liver metastasis were observed. The CD gene expression in each group was detected by RT-PCR. The histopathological changes, Apoptosis index. Results The target gene was expressed efficiently in metastatic liver tumors and was absent in normal liver tissues and in the stomach, lung, pancreas, small intestine and colorectal tissues. The natural life of the three groups were (25.80 ± 3.65), (34.27 ± 4.08) and (41.87 ± 3.91) d, respectively. The liver metastasis rates were 100.0% (15/15), 40.0% (6/15) and 13.3% (2/15). The average number of hepatic metastatic nodules was (2.93 ± 1.16), (0.80 ± 1.01) and (0.20 ± 0.56) respectively. The natural survival rate of the prodrug treatment group and the prodrug hyperthermia group was significantly longer than that of the control group (P <0.05). The liver metastasis rates of the three groups were statistically significant (all P <0.05) The apoptotic index (AI) were 4.59%, 9.87% and 17.4%, respectively. There were significant differences among the groups (P <0.05). Conclusion Tissue-specific CD / 5-FC thermochemotherapy can significantly inhibit the liver metastasis of colon cancer in nude mice.