Tunicamycin as a Novel Redifferentiation Agent in Radioiodine Therapy for Anaplastic Thyroid Cancer.
Int J Mol Sci
; 22(3)2021 Jan 22.
Article
em En
| MEDLINE
| ID: mdl-33499100
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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Glândula Tireoide
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Tunicamicina
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Carcinoma Anaplásico da Tireoide
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Radioisótopos do Iodo
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Antineoplásicos
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2021
Tipo de documento:
Article