摘要
Objective To investigate the efficiency of the cytosine deaminase adenoviral/5-fluorocytosine system on prostate cancer cell lines.Methods We used cell culture, infectivity and sensitivity tests, to observe bystander effect by animal tests.Results Established prostate cancer cell lines are eventually infectible by adenoviral vector. The ratio of vector/cell at which infection occurs depends on the specific cell line. The peak of expression of the transferred cytosine deaminase gene occurred in cells at different time, but persisted beyond 11 days. These prostate cell lines are sensitized to 5-fluorocytosine by infection with adenoviral vector carrying the cytosine deaminase gene. Only 5% of the LNCap and 10% of the RM-1 cells were infected and produced 100% cell death. In the animal test, there was significant inhibition of tumor growth at a ratio of 400 vector particles/cell with the systematic treatment of 5-fluorocytosine.Conclusions Adenoviral vector carrying a cytosine deaminase transcription unit can sensitize prostate cancer cell lines to 5-fluorocytosine. The system can significantly inhibit the growth of prostatic tumors in mice.
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。
