| Literature DB >> 33499100 |
Yoon Ju Choi1,2, Jae-Eon Lee3, Hyun Dong Ji1,2, Bo-Ra Lee3, Sang Bong Lee4, Kil Soo Kim3,5, In-Kyu Lee6,7,8, Jungwook Chin9, Sung Jin Cho9,7, Jaetae Lee1,7, Sang-Woo Lee1,7, Jeoung-Hee Ha2, Yong Hyun Jeon3,7.
Abstract
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. 125I uptake increased in TM-treated ATC cell lines, including BHT101 and CAL62, which was inhibited by KClO4, 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 18F-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.Entities:
Keywords: anaplastic thyroid cancer; radioiodine therapy; redifferentiation; sodium-iodide symporter; tunicamycin
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Year: 2021 PMID： 33499100 PMCID： PMC7865976 DOI： 10.3390/ijms22031077
Source DB: PubMed Journal: Int J Mol Sci ISSN： 1422-0067 Impact factor: 5.923