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目的 研究胞嘧啶脱氨酶 /5-氟胞嘧啶系统对前列腺癌细胞株的作用。方法 细胞培养 ,细胞转染 ,药物敏感性实验 ,观察旁观者效应 ,动物实验。结果 腺病毒载体可以转染所有已建立的前列腺癌细胞株 ,但是每种细胞株转染所要求的载体浓度以及暴露时间不同。转染的胞嘧啶脱氨酶基因在细胞内的表达高峰出现在不同的时间 ,但一直持续到 11天以后。腺病毒载体介导的胞嘧啶脱氨酶基因转染可以使前列腺癌细胞株提高对 5-氟胞嘧啶的敏感性。在LNCap和RM - 1细胞株中 ,只有 5%的细胞转染了胞嘧啶脱氨酶基因就可以引起 10 0 %的细胞杀伤效应。在动物实验中 ,用 40 0MOI转染过的肿瘤细胞建立小鼠皮下肿瘤并同时腹腔注射 5-氟胞嘧啶 ,可以有效的抑制肿瘤生长。结论 腺病毒载体介导的胞嘧啶脱氨酶基因转染可以提高前列腺癌细胞株对 5-氟胞嘧啶的敏感性 ,胞嘧啶脱氨酶 /5-氟胞嘧啶的联合应用能显著抑制小鼠肿瘤生长。
Objective To study the effect of cytosine deaminase / 5-fluorocytosine on prostate cancer cell lines. Methods Cell culture, cell transfection, drug sensitivity test, observe bystander effect, animal experiment. Results The adenoviral vector transfected all established prostate cancer cell lines, but the required vector concentration for each cell line transfected and the exposure time varied. Transfection of cytosine deaminase gene expression in the cell peak appeared at different times, but lasted until 11 days later. Adenovirus vector-mediated cytosine deaminase gene transfection can make prostate cancer cell lines to improve sensitivity to 5-fluorocytosine. In LNCap and RM - 1 cell lines, only 5% of cells transfected cytosine deaminase gene can cause 10% of the cell killing effect. In animal experiments, 40 MOI-transfected tumor cells were used to establish subcutaneous tumors of mice and intraperitoneal injection of 5-fluorocytosine, which can effectively inhibit tumor growth. Conclusions Adenovirus vector-mediated cytosine deaminase gene transfection can enhance the sensitivity of prostate cancer cell lines to 5-fluorocytosine. The combination of cytosine deaminase / 5-fluorocytosine can significantly inhibit the proliferation of prostate cancer cell lines Tumor growth.