scholarly journals Tunicamycin as a Novel Redifferentiation Agent in Radioiodine Therapy for Anaplastic Thyroid Cancer

2021 ◽  
Vol 22 (3) ◽  
pp. 1077
Author(s):  
Yoon Ju Choi ◽  
Jae-Eon Lee ◽  
Hyun Dong Ji ◽  
Bo-Ra Lee ◽  
Sang Bong Lee ◽  
...  

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.

Autophagy ◽  
2016 ◽  
Vol 12 (7) ◽  
pp. 1195-1205 ◽  
Author(s):  
Theo S. Plantinga ◽  
Marika H. Tesselaar ◽  
Hans Morreau ◽  
Eleonora P. M. Corssmit ◽  
Brigith K. Willemsen ◽  
...  

2007 ◽  
Vol 6 (7) ◽  
pp. 1130-1135 ◽  
Author(s):  
Hyun Joo Kim ◽  
Yong Hyun Jeon ◽  
Joo Hyun Kang ◽  
Yong Jin Lee ◽  
Kwang Kim ◽  
...  

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Chien-Chih Ke ◽  
Ya-Ju Hsieh ◽  
Luen Hwu ◽  
Fu-Hui Wang ◽  
Fu-Du Chen ◽  
...  

Anaplastic thyroid carcinoma (ATC) is one of the most deadly cancers. With intensive multimodalities of treatment, the survival remains low. ATC is not sensitive to131I 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 of131I 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.


2011 ◽  
Vol 96 (9) ◽  
pp. E1435-E1443 ◽  
Author(s):  
Garcilaso Riesco-Eizaguirre ◽  
Antonio De la Vieja ◽  
Irene Rodríguez ◽  
Soledad Miranda ◽  
Pilar Martín-Duque ◽  
...  

Abstract Context: Telomerase promoters (hTERT and hTR) are useful for transcriptional targeting in gene therapy models of cancer. Telomerase-driven expression of the sodium iodide symporter (NIS) in tumor cells has been successfully used as a reporter gene in vivo using positron emission tomography (PET) imaging. Objective: The aim of this study was to investigate the NIS-mediated therapeutic effect of telomerase promoters in a wide variety of human cancer cell lines. Design and Methods: Promoter fragments from either hTERT or hTR were used to drive the expression of NIS in cell lines derived from melanoma (M14), breast (MDA-MB-231), colon (HT-29), lung (H460), ovarian (OVCAR-3), and thyroid (TPC-1) carcinomas. Iodide uptake assays, protein immunodetection, and clonigenic assays were used to confirm NIS functional expression and the 131I-mediated cytopathic effect. Tumor xenografts in mice were infected with hTERT and hTR and then treated using radioiodide. Results: Both promoters were selectively active in cancer cells that were effectively killed by exposure to 131I. One single dose of 1 mCi 131I markedly suppressed tumor growth of melanoma-derived tumor xenografts compared with controls. This effect was more modest in colon cancer-derived xenografts in part due to the reduced infectivity and the tumor cystic nature. The therapeutic effect of hTR promoter was found to be stronger than that of hTERT promoter. Conclusions: These results demonstrate that telomerase-driven expression of NIS could potentially have applications for 131I therapy of a wide variety of cancers. Additionally, this is the first study to report NIS-mediated 131I therapy of melanoma tumors in vivo.


2011 ◽  
Vol 22 (12) ◽  
pp. 1563-1574 ◽  
Author(s):  
Kathrin Klutz ◽  
Michael J. Willhauck ◽  
Christian Dohmen ◽  
Nathalie Wunderlich ◽  
Kerstin Knoop ◽  
...  

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