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目的:探讨胞嘧啶脱氨酶基因对胃癌细胞的杀伤作用。方法:应用胞嘧啶脱氨酶(CD)基因,通过逆转录病毒载体转入人胃癌细胞M85中,经0.4 m g/m l的G418筛选阳性克隆的M85细胞产生杀伤作用同时,还对与其共培养的亲代M85细胞产生明显的杀伤作用,即“旁观者效应”。进一步将转基因M85细胞和未转基因M85细胞接种至裸鼠皮下,发现两者成瘤性无明显差异;前药5-FC对未转基因肿瘤的生长无影响,而对转基因肿瘤的生长明显抑制。结论:本研究为CD基因治疗胃癌向临床过渡提供了依据。
Objective: To investigate the killing effect of cytosine deaminase gene on gastric cancer cells. METHODS: CD gene was used to transform into human gastric cancer cell M85 by retroviral vector. The positive clone M85 cells were screened by G418 at 0.4 m g/ml for killing effect. The co-cultured parental M85 cells produced a marked killing effect, a “bystander effect.” Further, transgenic M85 cells and non-transgenic M85 cells were inoculated subcutaneously into nude mice and no significant difference in tumorigenicity was found between the two groups; 5-FC, a prodrug, had no effect on the growth of untransformed tumors but significantly inhibited the growth of transgenic tumors. Conclusion: This study provides a basis for CD gene therapy to clinical transition to gastric cancer.