胞嘧啶脱氨酶基因修饰的结肠癌细胞瘤苗抗肿瘤研究

目的 研究胞嘧啶脱氨酶（EC—CD）自杀基因修饰的结肠癌细胞瘤苗的抗肿瘤作用。方法 用含EC-CD基因的逆转录病毒质粒pLCDSN将人EC—CD基因转导入鼠结肠癌细胞株CT26，用G418进行筛选，得到抗性克隆CT26／CD，比较CT26／CD与野生型CT26的成瘤性，评价CT26／CD对野生型CT26细胞肝转移模型的治疗作用。结果 CT26／CD能在含0．6g／LG418的培养液中稳定生长；RT—PCR证实EC—CD基因在CT26／CD中表达；CT26／CD细胞对5-氟胞嘧啶（5-FC）的敏感性明显增加（P=0．000），且具有良好的旁观者效应；CT26／CD的成瘤性与野生型CT26相似（P=0．892）；CT26／CD联合5-FC对野生型CT26的肝转移有明显抑制作用，明显延长了荷瘤小鼠存活期（P=0．000）。结论 EC—CD基因修饰的结肠癌细胞瘤苗有一定的抗肿瘤作用。

Efficacy of antitumour colon cancer cell vaccine modified by eschrichia coli cytosine deaminase gene

Objectives To evaluate the efficacy of antitumour colon cancer cell vaccine modified by eschrichia coli cytosine deaminase (EC-CD).Methods Mouse colon cancer cell vaccine CT26/CD was established by gene modification using retrovirus plasmid pLCDSN.Its tumorigenicity and effect on liver metastasis model established with wild-type colon cancer were evaluated.Results CT26/CD was established successfully and proliferated in medium containing 0.6 g/L G418 stably.EC-CD gene expression on these mutant cells was confirmed by RT-PCR.These mutant cells were more sensitive to 5-fluorocytosine (5-FC) compared with the wild-type ones (P=0.000),and presented excellent bystander effect.CT26/CD had the same tumorigenicity as its parental cells (P=0.892).CT26/CD,combined with the prodrug 5-FC, could inhibit tumor progress and live metastasis,and prolonged the survival of the liver metastasis model animals (P =0.000).Conclusion The colon cancer cell vaccine modified by EC-CD presented anti-tumor effect in vivo,when treated with the prodrug.