重组hNIS病毒感染前列腺癌激素非依赖性细胞介导放射性碘治疗  

Radioiodide Treatment Mediated by Adenovirus Transfer of Human Sodium Iodide Symporter Gene into Androgen-independent Prostate Cancer

作　　者：黄蕤[1] 马晓娟[1] 李素平[1] 牟达[1] 龚日祥[2] 匡安仁[1] 

机构地区：[1]四川大学华西医院校医学科,成都610041 [2]四川大学华西医院甲状腺外科,成都610041

出　　处：《生物医学工程学杂志》2010年第5期1080-1084,共5页Journal of Biomedical Engineering

基　　金：国家自然科学基金面上项目资助(30670585)

摘　　要：为探讨重组人钠碘同向转运体(hNIS)基因的腺病毒感染激素非依赖性前列腺癌细胞介导放射性碘治疗的可能性,通过构建巨细胞病毒(CMV)启动的重组hNIS的腺病毒(Ad-CMV-NIS),感染激素非依赖型前列腺癌PC-3细胞,进行细胞体外和荷瘤裸鼠瘤体内分析,发现感染Ad-CMV-NIS的PC-3细胞能迅速摄取125I,其摄取能力约为空病毒转染组的120倍,摄碘功能可被NaClO4特异性抑制,125I在细胞内的半排期T1/2 efflux为26.7 min,131I可特异性杀死93.0%±3.8%的PC-3细胞。感染Ad-CMV-NIS的PC-3荷瘤裸鼠,肿瘤组织摄取125I 2 h达最高((16.30±8.72)%ID/g),125I在瘤体内的有效半衰期T1/2 effective为5.4 h,131I显像肿瘤显示清晰。结果表明,Ad-CMV-NIS感染可使PC-3细胞获得摄碘功能并被131I特异性杀死,肿瘤摄取高,为进一步体内治疗提供了有力的基础。This study sought to probe the feasibility of instituiting a radioiodide treatment for androgenindependent prostate cancer by adenovirus transfer of the hNIS gene.A recombinant adenovirus,Ad-CMV-NIS,that expressed the NIS gene under the control of cytomegalovirus（CMV） promoter was constructed.In vitro,after infection with Ad-CMV-NIS,PC-3 prostate cancer cells exhibited an uptake of perchlorate-sensitive iodide,approximately 120 times higher than that exhibited by negative control Ad-CMVGFP-infected cells.The half-time of efflux was 26.6min.Clonogenic assays demonstrated that Ad-CMV-NIS-infected cancer cells were selectively killed by exposure to 131I.In vivo,Ad-CMV-NIS infected tumors showed significant radioiodine accumulation（16.30±8.72）%ID/g at 2h post-injection） with an effective half-life of 5.4h.The tumor could be clearly visualized by 131I scintigraphy.These data indicate that infection with Ad-CMV-NIS is an efficient way to induce radioiodide uptake in vitro and in vivo,thus suggesting that NIS-based gene therapy has the potential for use in androgen-independent prostate cancer.

关 键 词：钠/碘同向转运体 重组腺病毒 放射性核素治疗 

分 类 号：R817.1[医药卫生—影像医学与核医学]