Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
J Oncol. 2011;2011:178967. doi: 10.1155/2011/178967. Epub 2011 Dec 15.
Anaplastic thyroid carcinoma (ATC) is one of the most deadly cancers. With intensive multimodalities of treatment, the survival remains low. ATC is not sensitive to (131)I therapy due to loss of sodium iodide symporter (NIS) gene expression. We have previously generated a stable human NIS-expressing ATC cell line, ARO, and the ability of iodide accumulation was restored. To make NIS-mediated gene therapy more applicable, this study aimed to establish a lentiviral system for transferring hNIS gene to cells and to evaluate the efficacy of in vitro and in vivo radioiodide accumulation for imaging and therapy. Lentivirus containing hNIS cDNA were produced to transduce ARO cells which do not concentrate iodide. Gene expression, cell function, radioiodide imaging and treatment were evaluated in vitro and in vivo. Results showed that the transduced cells were restored to express hNIS and accumulated higher amount of radioiodide than parental cells. Therapeutic dose of (131)I effectively inhibited the tumor growth derived from transduced cells as compared to saline-treated mice. Our results suggest that the lentiviral system efficiently transferred and expressed hNIS gene in ATC cells. The transduced cells showed a promising result of tumor imaging and therapy.
间变性甲状腺癌（ATC）是最致命的癌症之一。尽管采用了强化的多模式治疗方法，但其生存率仍然很低。由于钠碘转运体（NIS）基因表达的丧失，ATC 对（131）I 治疗不敏感。我们之前已经构建了一个稳定表达人 NIS 的 ATC 细胞系 ARO，恢复了碘的摄取能力。为了使 NIS 介导的基因治疗更具适用性，本研究旨在建立一种用于将 hNIS 基因转染到细胞中的慢病毒系统，并评估体外和体内放射性碘摄取用于成像和治疗的效果。制备含有 hNIS cDNA 的慢病毒以转导不摄取碘的 ARO 细胞。在体外和体内评估基因表达、细胞功能、放射性碘成像和治疗。结果表明，转导的细胞恢复表达 hNIS 并摄取比亲本细胞更多的放射性碘。与生理盐水治疗的小鼠相比，治疗剂量的（131）I 有效抑制了转导细胞来源的肿瘤生长。我们的结果表明，慢病毒系统可有效地将 hNIS 基因转染和表达于 ATC 细胞。转导的细胞在肿瘤成像和治疗方面显示出有希望的结果。
