靶向调控UPRT/5-FU自杀基因系统对前列腺癌细胞旁观者效应的研究  

Bystander Effect of Target-regulated Uracil Phosphoribosyltransferase/5-Fluorouracil Suicide Gene System on Prostate Cancer Cell

作　　者：赵福军[1] 李虹[1] 曾浩[1] 魏强[1] 李响[1] 

机构地区：[1]四川大学华西医院泌尿外科

出　　处：《四川大学学报（医学版）》2008年第3期394-397,共4页Journal of Sichuan University(Medical Sciences)

基　　金：四川省科技厅基金(04JY029-082-1)资助

摘　　要：目的研究前列腺特异性膜抗原(PSMA)增强子(enhancer)/启动子(promoter)靶向性调控尿嘧啶磷酸核糖转移酶(UPRT)/5-氟尿嘧啶(5-FU)自杀基因系统对前列腺癌细胞株的旁观者效应。方法应用自行构建PSMA启动子/增强子靶向性调控的UPRT基因真核表达质粒pPSMA enhancer/promoter-UPRT,脂质体介导转染质粒,并应用G418进行稳定表达UPRT基因的前列腺癌细胞株的筛选。转染质粒pPSMA enhancer/promoter-UPRT的前列腺癌细胞和非转染细胞按不同比例混合培养,UPRT/5-FU自杀基因系统配给,MTT法检测其对前列腺癌细胞杀伤的旁观者效应。结果成功筛选稳定表达UPRT基因的前列腺癌细胞株;通过转染细胞和非转染细胞按照不同比例混合,结果显示该自杀基因系统并没有明显的旁观者效应,随着转染比例的增多,细胞增殖抑制率也逐渐增加,没有出现跳跃明显性增加。结论UPRT可以使5-FU快速转化毒性物质,发挥细胞毒作用,但发挥细胞毒杀作用中的旁观者效应不明显。Objective To study the bystander effect of Uracil Phosphoribosyltransferase （UPRT）/5- fluorouracil （5-FU） suicide gene system, which is regulated by PSMA enhancer/promoter, on prostate cancer cell. Methods Mediated by liposome, pPSMA enhancer/promoter-UPRT was transferred into prostate cancer line. And the cell line that could express UPRT gene stably was selected with antibiotic G418. The various percentages of prostate cancer cells（LNCaP） transfected and non-transfected were mixed to observe the bystander effect of suicide gene system UPRT/5-FU. Results The cell line that could express UPRT gene stably was screened successfully. With the LNCaP cells that expressed UPRT gene becoming more and more, the cell survival rate went down gradually. No obvious bystander effect showed after using UPRT/5-FU suicide gene system. Conclusion pPSMA enhancer/promoter-UPRT/5-FU suicide gene system kills LNCaP cells in target. UPRT can transform 5-FU into toxic metabolites quickly and play the role of cytotoxicity. However, the bystander effect of UPRT/5-FU isn＇t obvious. It will be studied further for UPRT/5-FU how to strengthen the cytotoxic role by improving the bystander effect.

关 键 词：尿嘧啶磷酸核糖转移酶 5-氟尿嘧啶 自杀基因 旁观者效应 前列腺癌 

分 类 号：R737.25[医药卫生—肿瘤]