Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41566, Korea.
Department of pharmacology, School of Medicine, Kyungpook National University, Daegu 41405, Korea.
Int J Mol Sci. 2021 Jan 22;22(3):1077. doi: 10.3390/ijms22031077.
The silencing of thyroid-related genes presents difficulties in radioiodine therapy for anaplastic thyroid cancers (ATCs). Tunicamycin (TM), an N-linked glycosylation inhibitor, is an anticancer drug. Herein, we investigated TM-induced restoration of responsiveness to radioiodine therapy in radioiodine refractory ATCs. I uptake increased in TM-treated ATC cell lines, including BHT101 and CAL62, which was inhibited by KClO, a sodium-iodide symporter (NIS) inhibitor. TM upregulated the mRNA expression of iodide-handling genes and the protein expression of NIS. TM blocked pERK1/2 phosphorylation in both cell lines, but AKT (protein kinase B) phosphorylation was only observed in CAL62 cells. The downregulation of glucose transporter 1 protein was confirmed in TM-treated cells, with a significant reduction in F-fluorodeoxyglucose (FDG) uptake. A significant reduction in colony-forming ability and marked tumor growth inhibition were observed in the combination group. TM was revealed to possess a novel function as a redifferentiation inducer in ATC as it induces the restoration of iodide-handling gene expression and radioiodine avidity, thereby facilitating effective radioiodine therapy.
甲状腺相关基因沉默给间变性甲状腺癌（ATC）的放射性碘治疗带来了困难。衣霉素（TM）是一种 N-连接糖基化抑制剂，也是一种抗癌药物。在此，我们研究了 TM 诱导放射性碘难治性 ATC 对放射性碘治疗反应性恢复的作用。TM 处理的 ATC 细胞系（包括 BHT101 和 CAL62）中的碘摄取增加，这一过程被钠-碘转运体（NIS）抑制剂高氯酸钾（KClO）抑制。TM 上调了碘处理基因的 mRNA 表达和 NIS 的蛋白表达。TM 阻断了两种细胞系中 pERK1/2 的磷酸化，但仅在 CAL62 细胞中观察到 AKT（蛋白激酶 B）的磷酸化。TM 处理的细胞中葡萄糖转运蛋白 1 蛋白下调，F-氟脱氧葡萄糖（FDG）摄取显著减少。联合组中集落形成能力显著降低，肿瘤生长明显抑制。TM 具有诱导 ATC 碘处理基因表达和放射性碘摄取恢复的新型分化诱导作用，从而促进有效的放射性碘治疗，因此具有新的作用。
