Abstract
PurposeThe 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.MethodsA 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 99mTc 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 99mTc 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.ConclusionsThe radionuclide imaging and therapy technique for NPC hNIS-transfected cell lines can provide a new therapy strategy for monitoring and treatment of NPC.
Highlights
Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Southern and Southeast Asia, with an annual incidence of 10–30 per 100,000 people
After liposome-mediated transfection of CNE-2 cells with the pCMV-Tag2-human sodium/iodide symporter (hNIS) plasmid, the stable CNE-2-hNIS transfected cell line was established by geneticin selection, and the expression of hNIS in cells was detected by hNIS monoclonal antibody (Fig. 1a)
CNE-2-hNIS cells accumulated high amounts of radioiodide, which were completely inhibited by the addition of perchlorate, whereas the control CNE-2 cell line did not (Fig. 1b)
Summary
Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Southern and Southeast Asia, with an annual incidence of 10–30 per 100,000 people. NIS is an integral membrane protein located on the basolateral surface of the thyroid follicular cells that mediate the uptake and concentration of iodide into the thyroid gland [3, 4]. NIS gene transfection offered a new approach to treatment of extrathyroidal malignancies. While cloning of the NIS gene can be transfected into different tumor cell lines, the uptake of radioactive iodide should partially inhibit cells’ growth. 131I targeted therapy mediated by transfected NIS uses the β-rays emitted during 131I decay. The exact biological mechanism to achieve 131I targeted therapy in NIS-transfected non-thyroid cancer has not been established
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