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转染人钠/碘同向转运体基因用于鼻咽癌放射性核素显像及治疗的实验研究

Experimental study of nasopharyngeal carcinoma radionuclide imaging and therapy using transferred human sodium/iodide symporter gene.

作者信息

Zhong Xing, Shi Changzheng, Gong Jian, Guo Bin, Li Mingzhu, Xu Hao

机构信息

Department of Medical Imaging Center, First Affiliated Hospital, Jinan University, Guangzhou 510630, China.

Department of Nuclear Medicine, First Affiliated Hospital, Jinan University, Guangzhou 510630, China.

出版信息

PLoS One. 2015 Jan 23;10(1):e0117053. doi: 10.1371/journal.pone.0117053. eCollection 2015.

Abstract

PURPOSE

The aim of this study was to design a method of radionuclide for imaging and therapy of nasopharyngeal carcinoma (NPC) using the transferred human sodium/iodide symporter (hNIS) gene.

METHODS

A stable NPC cell line expressing hNIS was established (CNE-2-hNIS). After 131I treatment, we detected proliferation and apoptosis of NPC cells, both in vitro and vivo. In vivo, the radioactivity of different organs of nude mice was counted and (99m)Tc imaging using SPECT was performed. The apparent diffusion coefficient (ADC) value changes of tumor xenografts were observed by diffusion-weighted magnetic resonance imaging (DW-MRI) within 6-24 days of 131I treatment. The correlation of ADC changes with apoptosis and proliferation was investigated. Post-treatment expression levels of P53, Bax, Bcl-2, Caspase-3, and Survivin proteins were detected by western blotting.

RESULTS

131I uptake was higher in CNE-2-hNIS than in CNE-2 cells. The proliferation and apoptosis rate decreased and increased respectively both in vitro and vivo in the experimental group after 131I treatment. The experimental group tumors accumulated (99m)Tc in vivo, leading to a good visualization by SPECT. DW-MRI showed that ADC values increased in the experimental group 6 days after treatment, while ADC values were positively and negatively correlated with the apoptotic and Ki-67 proliferation indices, respectively. After treatment, CNE-2-hNIS cells up-regulated the expression of P53 and Survivin proteins and activated Caspase-3, and down-regulated the expression of Bcl-2 proteins.

CONCLUSIONS

The radionuclide imaging and therapy technique for NPC hNIS-transfected cell lines can provide a new therapy strategy for monitoring and treatment of NPC.

摘要

目的

本研究旨在设计一种利用转染人钠/碘同向转运体(hNIS)基因的放射性核素对鼻咽癌(NPC)进行成像和治疗的方法。

方法

建立稳定表达hNIS的NPC细胞系(CNE-2-hNIS)。经131I处理后,我们在体外和体内检测NPC细胞的增殖和凋亡情况。在体内,对裸鼠不同器官的放射性进行计数,并使用单光子发射计算机断层扫描(SPECT)进行(99m)Tc成像。在131I处理后的6 - 24天内,通过扩散加权磁共振成像(DW-MRI)观察肿瘤异种移植的表观扩散系数(ADC)值变化。研究ADC变化与凋亡和增殖的相关性。通过蛋白质免疫印迹法检测治疗后P53、Bax、Bcl-2、Caspase-3和Survivin蛋白的表达水平。

结果

CNE-2-hNIS细胞对131I的摄取高于CNE-2细胞。131I处理后,实验组体外和体内的增殖率降低,凋亡率分别升高。实验组肿瘤在体内积聚(99m)Tc,通过SPECT可实现良好的可视化。DW-MRI显示,治疗后6天实验组的ADC值升高,而ADC值分别与凋亡指数和Ki-67增殖指数呈正相关和负相关。治疗后,CNE-2-hNIS细胞上调P53和Survivin蛋白的表达并激活Caspase-3,下调Bcl-2蛋白的表达。

结论

针对NPC hNIS转染细胞系的放射性核素成像和治疗技术可为NPC的监测和治疗提供一种新的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db68/4304840/334edea95730/pone.0117053.g001.jpg

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