构建了以癌胚抗原(CEA)基因启动子控制的HSV-TK和ECCD的表达质粒PCEA-TK和pCEA-CD. 将它们分别与pSV2-neo共转染人结肠癌细胞株LoVo和人宫颈癌细胞株HeLa. G418筛选得到细胞克隆LoVo/CEA-TK、toVo/CEA-CD、HeLa/CEA-TK和HeLa/CEA-CD. 与野生型LoVo细胞相比, LoVo/CEA-TK和LoVo/CEA-CD形态无明显改变, 生长曲线也相似, 但对GCV或5-FC的细胞毒的敏感性分别提高了2000倍或700倍.而HeLa/CEA-TK(或HeLa/CEA-CD)仍对低浓度GCV(或5-FC)不敏感. 以上结果显示了应用组织专一性表达的自杀基因治疗人结肠癌的可能性.
The expression plasmid PCEA-TK or pCEA-CD was constructed by ligating the CEA gene promoter to suicide gene such as HSV-TK (herpes simplex virus thymidine kinase) gene or EC-CD (E. coli cytosine deaminase) gene. A human colorectal carcinoma cell line LoVo or a human uterine cervical cancer cell line HeLa was co-transfected with pSV2-neo and PCEA-TK (or PCEA-CD). After selection with G418, the transgenetic cell clones (hoVo/CEA-TK,LoVo/CEA-CD, HeLa/CEA-TK and HeLa/CEA-CD) were obtained. There was no significant difference in either morphology or cell growth curve between suicide gene transduced cells and wild type cells. But LoVo/CEA-TK (or LoVo/CEA-CD) cells were 2000(or 700) times more sensitive to the cytotoxicity of prodrug ganciclovir(or S-Fluorocytosine)than parental LoVo cells. However, HeLa/CEA-TK or HeLa/CEA-CD cells were still resistant to Ganciclovir (or 5-Fluorocytosine). These results showed the possibility of gene therapy for human colorectal carcinoma by cell type-specific expression of suicide genes.
蒋琼,戈凯,许德华,郑仲承,刘新垣.组织专一性表达自杀基因治疗人结肠癌的研究[J].生物化学与生物物理进展,1996,23(4):376-378
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