Asan Institute for Life Science, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul 138-736, South Korea.
Nucl Med Biol. 2012 Nov;39(8):1275-80. doi: 10.1016/j.nucmedbio.2012.08.007. Epub 2012 Sep 18.
Patients with metastatic thyroid cancers that do not uptake iodine need effective therapeutic option. Differentiation-inducing agents have been tried to restore functional expression of sodium iodide symporter (NIS) without success. Our objective was to assess the effect of alpha-lipoic acid (ALA), known as potential antioxidant, on expression of sodium iodide symporter in thyroid cancer cells.
Human thyroid cancer-derived cell lines, TPC-1, were treated with ALA, and changes in NIS mRNA and protein expression were measured. ALA's effect on NIS gene promoter was evaluated, and functional NIS expression was assessed by iodide uptake assay.
Treatment with ALA increased NIS mRNA expression up to ten folds of control dose-dependently after 24 h of exposure. ALA increased NIS promoter activity, and increased iodide uptake by 1.6 fold. ALA induced expression of NIS protein, but had no significant effect on the plasma membrane trafficking. ALA increased phosphorylation of CREB and nuclear translocation of pCREB, and co-treatment of ALA and trichostatin A increased iodide uptake by three folds in TPC-1 cells.
ALA is a potential agent to increase NIS transcription in TPC-1. It could be used as an adjunctive agent to increase efficacy of radioiodine therapy if combined with a strategy to increase NIS protein trafficking to cell membrane.
无法摄取碘的转移性甲状腺癌患者需要有效的治疗选择。分化诱导剂已被尝试用于恢复钠碘转运体（NIS）的功能表达，但均未成功。我们的目的是评估α-硫辛酸（ALA）对甲状腺癌细胞中钠碘转运体表达的影响。
用 ALA 处理人甲状腺癌细胞系 TPC-1，并测量 NIS mRNA 和蛋白表达的变化。评估 ALA 对 NIS 基因启动子的影响，并通过碘摄取测定评估功能性 NIS 表达。
暴露 24 小时后，ALA 以剂量依赖性方式将 NIS mRNA 表达增加至对照的十倍以上。ALA 增加了 NIS 启动子活性，并使碘摄取增加了 1.6 倍。ALA 诱导 NIS 蛋白表达，但对质膜转运没有明显影响。ALA 增加了 CREB 的磷酸化和 pCREB 的核转位，并且 ALA 和曲古抑菌素 A 的共同处理使 TPC-1 细胞中的碘摄取增加了三倍。
ALA 是增加 TPC-1 中 NIS 转录的潜在药物。如果与增加 NIS 蛋白向细胞膜转运的策略结合使用，它可以作为增加放射性碘治疗效果的辅助药物。
