摘要
目的通过荷瘤裸鼠实验探讨hNIS基因转染介导^131I治疗鼻咽癌的可行性及其作用机制。方法利用转染hNIS的鼻咽癌CNE-2-hNIS细胞（实验组）和未转染hNIS的CNE-2细胞（对照组）分别建立荷鼻咽癌裸鼠模型，对裸鼠行^131I体内分布实验和^99Tc^m显像，观察^131I治疗前后实验组和对照组移植瘤体积变化。采用原位末端标记法（TUNEL）检测治疗前和治疗后第6天移植瘤细胞的凋亡率，以免疫组织化学法检测治疗前后移植瘤半胱氨酸蛋白酶3（caspase3）和细胞增殖相关核抗原Ki67的表达。用SPSS13．0软件对样本均数间差异行t检验。结果成功构建荷CNE-2-hNIS裸鼠移植瘤与荷CNE-2裸鼠移植瘤模型。实验组移植瘤摄取^131I能力增强，1h达高峰，摄取率达（20．284-0．15）％，^131I生物半衰期为1．56h。显像结果示实验组移植瘤有放射性浓聚，1．5～2h移植瘤摄取”Tc“0f达高峰，肿瘤显影清晰，而对照组移植瘤未见显影。实验组移植瘤治疗前体积为（0．44±0．04）cm^3，^131I治疗后第24天体积为（0．97±0．08）cm^3；而对照组相应值分别为（0．45±0．06）和（2．98±0．16）cm^3，治疗后实验组移植瘤体积与对照组比较，差异有统计学意义（t=19．46，P〈0．01）。^131I治疗后第6天实验组移植瘤凋亡率[（0．66±0．07）％]增高，caspase3阳性率[（0．56±0．14）％]增高，Ki67增殖指数[（0．22±0．10）％]降低，与治疗前[各指标依次为（0．08±0．06）％、（0．13±0．04）％和（0．65±0．11）％]比较差异有统计学意义（t值分别为10．89、5．12和5．01，均P〈0．05）。结论荷瘤裸鼠实验表明，hNIS转染鼻咽癌在体内可明显摄取^131I、^131I及^99Tc^m，可进行放射性核素显像和治疗；^131I能有效抑制hNIS转染鼻咽癌细胞的增殖，诱导其凋亡。
Objective To explore the feasibility of 131I radiotherapy mediated by hNIS gene trans- fection in nasopharyngeal carcinoma （NPC）. Methods NPC xenograft models were established with CNE- 2-hNIS cells （experimental group） and CNE-2 cells （control group）. Radioactivity of different organs of nude mice was counted at 0.5, 1,2, 6 and 24 h after intraperitoneal injection of 125I using a gamma counter. 99TcmO4 imaging was also performed in nude mice. Changes in the xenograft tumor volume were ob- served after 131I treatment in the experimental group and control group. Cell apoptosis was detected after 131I treatment by the terminal oxynucleotidyl transferase mediated dUTP biotin nick end labeling （TUNEL） method and caspase 3 and Ki67 expressions measured with immunohistochemistry of the tumor tissue. Statis- tical analysis was performed using SPSS 13.0 software, and the mean values between groups were compared using t test. Results CNE-2-hNIS and CNE-2 NPC xenografts were established successfully in nude mice. Biodistribution of 125I in tumor-bearing nude mice showed enhanced tumor uptake of 125I in the experimental group, with peak uptake at 1 h （ （20.28 ±0.15）% ）. The biological half-life of ^125I in the tumors transfect- ed with hNIS was about 1.56 h. Imaging studies showed that the tumors in the experimental group accumu- lated 99TcmO4- with a peak at 1.5 -2 h, whereas the control tumors were not visualized. The mean volume of the experimental xenograft tumors was （0.44 ± 0.04） cm3 before in I treatment and increased to （0.97± 0.08） cm3 after 1311 treatment. However, the volume of the control xenografts was （0.45± 0.06） cm3 before 131I treatment and （2.98 ±0.16） cm3 after 131I treatment. The tumor volume of the experimental group was significantly smaller compared with that of the control group after ~311 treatment （ t = 19.46, P 〈 0.01 ）. A higher apoptotic index and caspase 3 positive rate as well as lower Ki67 proliferation index were observed in the experimental group after 131I treatment （（0.66 ± 0.07）%, （0.56 ± 0.14）%, （0.22± 0.10）%, respectively） compared with those before ^131I treatment （ （0.08±0.06） %, （0. 13 ± 0.04） % and （0.65±0.11 ） %, t = 10.89, 5.12, 5.01, respectively, all P 〈 0.05）. Conclusions The transfected hNIS gene may mediate uptake of 125I, 131I and 99Tcm 04 in NPC xenografts and thus provides potential for radionuclide imaging and radiotherapy for NPC. 131i may effectively inhibit proliferation and induce apoptosis of NPC xen- ografts transfected with the hNIS gene.
出处
《中华核医学与分子影像杂志》
CSCD
北大核心
2012年第6期452-456,共5页
Chinese Journal of Nuclear Medicine and Molecular Imaging
基金
广东省科技计划项目--承担政府特定任务项目（20118061200028）
广东省重大科技计划项目（2003A3080501）
关键词
鼻咽肿瘤
肿瘤移植
转染
钠
碘转运体
放射性核素显像
近距离放射疗法
小鼠
裸
Nasopharyngeal neoplasms
Neoplasm transplantation
Transfection
Sodium/iodide symporter
Radionuclide imaging
Brachtherapy
Mice, nude
作者简介
通信作者：徐浩，Email：txh@jnu．edu．cn
