hNIS基因转染介导Hela细胞移植瘤放射性核素显像和治疗的实验研究

The experimental study of radionuclide imaging and treatment of cervical cancer mediated by hNIS gene transfection

目的 利用131I对转染hNIS基因的宫颈癌Hela-NIS（＋）细胞移植瘤进行显像及治疗实验研究,评价hNIS基因转染介导131I治疗宫颈癌的可行性.方法 （1）利用Hela-NIS（＋）细胞和未转染hNIS的Hela细胞分别建立荷宫颈癌裸鼠模型,进行131I及99TcmO4-显像,观察移植瘤的显影情况,并计算移植瘤部位与对侧相同部位的T/B比值.（2）通过腹腔注射法观察比较74,111和148 MBq131I对荷Hela-NIS（＋）宫颈癌裸鼠移植瘤的抑制作用,另设不行任何治疗的对照组.用SPSS 13.0软件,样本均数间差异行t检验.结果 （1）成功构建荷Hela-NIS（＋）裸鼠移植瘤与荷Hela裸鼠移植瘤模型.131I显像示荷Hela-NIS（＋）裸鼠移植瘤部位明显放射性浓聚,注射后8 h T/B比值最高达17.34,而未转染hNIS基因的荷Hela裸鼠移植瘤部位始终未见明显的放射性浓聚.99TcmO4-显像示荷Hela-NIS（＋）裸鼠移植瘤部位在注射后25 h内持续放射性浓聚.（2）经不同剂量的131I治疗后2～3周起,各治疗组荷Hela-NIS（＋）裸鼠移植瘤生长开始受到抑制,移植瘤体积有不同程度缩小.111MBq组和148 MBq组的移植瘤抑制率差异无统计学意义（t=0.13～2.17,P＞0.05）,但二者均明显高于74 MBq组的移植瘤抑制率（t=2.74～5.75,P＜0.05）.对照组荷Hela-NIS（＋）裸鼠移植瘤持续生长.结论 荷Hela-NIS（＋）宫颈癌裸鼠移植瘤可明显聚集131I及99TcmO4-,且在较长时间内持续清晰显影;131I体内治疗效果显著.

Objective To explore the feasibility of imaging and treatment of cervical cancer xenograft model using 131I mediated by hNIS gene transfection. Methods The cervical cancer xenograft models were established with Hela-NIS（ ＋） cells and Hela cells, respectively. Five Hela-NIS（ ＋） xenograft models and five Hela xenograft models were dynamically imaged at 0.5, 1, 2, 4, 8, 16 and 20 h postinjection of 131I（7.4 MBq）. Five Hela-NIS（ ＋） xenograft models were imaged at 0. 5,1,2,4,8,16, 20 and 25 h postinjection of 99TcmO4-（11.1 MBq）. Twenty Hela-NIS（ ＋） cervical cancer xenograft models were randomly divided into four groups： Three 131I treating groups and one control group. The therapeutic effects of 131I at threelevels （74,111,148 MBq） were investigated following intraperitoneal injection. Results Hela-NIS（ ＋）human cervical cancer xenografts were established successfully in nude mice. The Hela-NIS（ ＋） xenografts significantly accumulated radioactivity after intraperitoneal injection of 131I, and the radioactivity was persistently present until 20 h postinjection, but Hela xenografts had no radioactive accumulation. The T/B value of the Hela-NIS（ ＋） xenografts reached 17.34 at 8 h postinjection. The imaging with 99TcmO4- showed that the radioactivity was persistently present in Hela-NIS（ ＋） xenografts for almost 25 h. The Hela-NIS（ ＋）xenografts shrinked after 131I treatment. The inhibition ratios of tumor growth in 111 MBq and 148 MBq groups were both significantly higher than that of 74 MBq group （t： 2.74-5.75, P 〈0.05）. Conclusions Hela-NIS（ ＋） cervical cancer xenografts in nude mice could persistently accumulate 131I and 99TcmO4- and could be treated successfully with 131 I. 131 I treatment mediated by hNIS gene transfection could be a promising cancer treatment method.