目的 :研究自杀基因胞嘧啶脱氨酶(cytosine deaminase,CD)基因转染的小鼠骨髓源性内皮祖细胞(endothelial progenitor cells,EPCs)联合酶前体药物5-氟胞嘧啶(5-l uorocytosine,5-Fc)对小鼠H22细胞原位移植性肝细胞癌的抑制作用。方法 :采用Polybrene技术将含有CD基因的慢病毒重组载体plenti6.3-EGFPCD感染至EPCs,倒置显微镜下观察转染CD基因的EPCs上清液和5-Fc共处理后H22细胞的数目和形态变化。用转染CD基因的EPCs和5-Fc联合治疗H22原位移植肝细胞癌模型小鼠,磁共振扫描监测肿瘤体积变化,TUNEL法检测肿瘤细胞凋亡,蛋白质印迹法检测移植瘤组织中CD蛋白表达。结果 :经CD基因转染的EPCs上清液联合5-Fc处理后,H22细胞增殖数量明显减少。转染CD基因的EPCs联合5-Fc治疗组小鼠肿瘤生长抑制率达(47.29±5.81)%,肿瘤细胞凋亡指数为(39.98±5.13)%,均明显高于空载体对照组(P<0.05)。结论 :CD基因修饰的EPCs联合5-Fc给药可有效抑制小鼠原位移植肝细胞癌的细胞增殖,并诱导肿瘤细胞凋亡。 OBJECTIVE: To study the effects of suicide gene CDK (murine bone marrow-derived endothelial progenitor cells, EPCs) combined with 5-l uorocytosine , 5-Fc) inhibits orthotopic transplantation hepatocellular carcinoma in mouse H22 cells. Methods: The lentiviral recombinant plasmid plenti6.3-EGFPCD containing CD gene was infected into EPCs by Polybrene technique. The numbers and morphological changes of H22 cells co-treated with EPCs supernatant and 5-Fc transfected with CD gene were observed under inverted microscope . EPCs transfected with CD gene and 5-Fc were used to treat H22 orthotopic hepatocellular carcinoma model mice. The changes of tumor volume were monitored by MRI. The apoptosis of tumor cells was detected by TUNEL method. CD protein expression. Results: The proliferation of H22 cells was significantly reduced by EPCs supernatants transfected with CD gene combined with 5-Fc. The inhibitory rate of tumor growth in EPCs transfected with CD gene combined with 5-Fc was (47.29 ± 5.81)%, and the apoptotic index of tumor cells was (39.98 ± 5.13)%, which were significantly higher than those in control group (P < 0.05). CONCLUSION: CD gene-modified EPCs combined with 5-Fc can effectively inhibit cell proliferation and induce apoptosis of hepatocellular carcinoma in mice.