Human sodium/iodide symporter gene induced iodine uptake in human lung adenocarcinoma via baculovirus
Human sodium/iodide symporter gene induced iodine uptake in human lung adenocarcinoma via baculovirus
复制标题
人钠/碘同向转运蛋白基因通过杆状病毒诱导人肺腺癌的碘摄取
DOI：
10.13538/j.1001-8042/nst.21.99-105
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发表时间：
2010
影响因子：
2.8
通讯作者：
Li Biao
中科院分区：
文献类型：
--
作者：
Guo Rui;Zhang Yifan;Liang Sheng;Zhang Miao;Jiang Xufeng;Li Biao
为研究杆状病毒介导的人钠碘转运体（hNIS）对人肺腺癌碘摄取的影响，构建了含hNIS基因的重组杆状病毒（Bac-CMV-hNIS）。在体外，杆状病毒感染的A549细胞积累约27倍以上的125 I比未感染的细胞。125 I摄取是最大的细胞孵育30分钟后，和流出的放射性是快速的，与50%的损失后，在第一个2分钟内，含125 I的培养基已被替换为非放射性介质。在高氯酸钠的存在下的竞争实验表明，125 I摄取的剂量依赖性下降。Bac-CMV-hNIS感染的肿瘤细胞通过暴露于131 I被选择性地杀死，如通过克隆形成测定所揭示的。在裸鼠体内，Bac-CMV-hNIS感染的A549细胞在131 I给药后1h的放射性核素显像显示，131 I的累积量高于对照组。杆状病毒介导的hNIS基因在体外和体内均能诱导A549细胞的碘转运，显示了这种新型肿瘤基因显像方法的潜力。但在体内显示放射性从肿瘤中快速流出，体内治疗试验显示无效果迹象。
To investigate human sodium/iodide symporter (hNIS) induced iodine uptake in human lung adenocarcinoma via baculovirus, a recombinant baculovirus encoding hNIS gene was constructed under the control of CMV promoter (Bac-CMV-hNIS). In vitro, baculovirus infected A549 cells accumulated about 27 times more 125I than that of noninfected cells. The 125I uptake was maximal after 30-min incubation of the cells, and efflux of the radioactivity was rapid, with 50% lost during the first 2 min after 125I-containing medium had been replaced by nonradioactive medium. Competition experiments in the presence of sodium perchlorate revealed a dose-dependent decrease of 125I uptake. Bac-CMV-hNIS infected tumor cells were selectively killed by exposure to 131I, as revealed by clonogenic assays. In nude mice, Bac-CMV-hNIS infected A549 cells accumulated more 131I than that of the control monitored by 1-h scintigraphy after 131I administration. The transduction of hNIS gene through baculovirus is sufficient to induce iodine transporting in A549 cells in vitro and in vivo, outlining the potential of this novel tumor gene imaging approach. But a rapid efflux of radioactivity from the tumor was shown in vivo and the in vivo therapy test showed no sign of effect.