腺病毒介导钠/碘泵基因靶向治疗胰腺癌  

MUC1 promoter drives hNIS genes targeting expression In pancreatic carcinoma cells

作　　者：周泉波[1] 陈汝福[1] 李志花[2] 田芬[3] 周嘉嘉[1] 陈积圣[1] 

机构地区：[1]中山大学附属第二医院肝胆外科,广州510120 [2]中山大学附属第二医院肿瘤科,广州510120 [3]中山大学基础医学院组胚教研室

出　　处：《中华实验外科杂志》2007年第10期1212-1214,共3页Chinese Journal of Experimental Surgery

基　　金：广州市科委资助项目(2007Z3-D2061);广东省医学科学研究基金(A2005228);国家高科技计划(863)资助项目(2002AA214061);广东省自然科学基金(2003A031700)

摘　　要：目的观察0.8 kb的Mucin 1黏蛋白(MUC1)启动子驱动人钠/碘同向转运体(hNIS)基因在胰腺癌细胞靶向表达,评估其吸收碘的能力及结合放射碘治疗胰腺癌的效果。方法采用双质粒脂质体共转染方法获得复制缺陷型腺病毒Ad/MUC1/hNIS。Ad/MUC1/hNIS体外感染细胞,通过免疫荧光染色方法及细胞^(125)I的吸收试验检测hNIS在细胞的靶向表达及吸碘功能。构建鼠Capan-2胰腺癌模型,瘤内注射病毒后,结合^(131)I治疗,观察对移植瘤生长的抑制作用。结果hNIS仅在MUC1阳性的CAPAN-2和SW1990细胞的胞膜靶向表达,且有高的^(125)I吸收能力,分别较对照组提高20.5和13倍。Ad/MUC1/hNIS感染的肿瘤结合^(131)I治疗能抑制肿瘤生长,肿瘤体积减小到原来的83%。结论0.8 kb的MUC1启动子能驱动hNIS基因在MUC1阳性的胰腺癌细胞靶向表达,结合^(131)I治疗后能抑制胰腺癌的生长。To investigate the potential for treatment of pancreatic cancer by creating a construct containing NIS under the control of the 0.8kb-MUC1 promoter and transfecting it into pancreatic cancer cells both in vitro and in vivo. Methods Replication-deficient human recombinant adenovirus Ad. MUC1/NIS was produced by the two plasmid rescue method. The iodide uptake assays and immunofluorescence were used to confirm NIS expression and function in vitro. After nude mice model implanted subcutaneously with Capan-2 was established, the implanted tumor was intratumorally infected with Ad. MUC1/NIS, mice were administered with an i.p. dose of ^131I, and tumor volume was recorded weekly. Results A 23 and 15.5-fold increase in iodide uptake was observed in the infected MUCl-positive Capan-2 and SW1990 with no significant increase observed in MUCl-negative Hela cells. Strong membranetargeted immunofluorescent activity was also only detected in MUCl-positive cells. Administration of a therapeutic dose of ^131I resulted in an 17% reduction in volume for Ad/MUC1/NIS-infected tumor, whereas control tumors continued to increase in size （ 〉 200% ）. Condtltsion The 0.8kb-MUC1 promoter is capable of directing efficient and selective expression of the NIS gene in MUCl-positive pancreatic tumor cells, and also can inhibit the growth of tumor.

关 键 词：MUC1启动子 钠/碘同向转运体 胰腺肿瘤 碘放射性同位素 基因治疗 

分 类 号：R735.9[医药卫生—肿瘤]