Effects of a Phosphoinositide-3-Kinase Inhibitor on Anaplastic Thyroid Cancer Stem Cells

Document Type : Research Articles

Authors

1 Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

2 Cellular and Molecular Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

3 Stem Cell Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

4 Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

5 Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

6 Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Abstract

 
Background: Thyroidectomy, radioactive iodine therapy, chemotherapy, or their combination are treatments of choice for thyroid cancers. However, cancer stem cells (CSCs) may become resistant to therapy, and mutations in somatic genes affect radioiodine uptake. This study determined the effect of a phosphoinositide-3-kinase (PI3K) inhibitor on anaplastic thyroid CSCs. Materials and Methods: The magnetic-activated cell sorting assay was used for segregating CD133-positive CSCs from three anaplastic thyroid carcinoma (ATC) cell lines (C643, SW1736, and 8305C). After confirming the cells’ purity by flow cytometry, they were treated with 5, 10, 20, or 25 μM LY294002, a PI3K inhibitor, and then evaluated at 24 and 48 h. The sodium-iodide symporter (NIS) mRNA level was determined using the quantitative real-time polymerase chain reaction. NIS protein expression was evaluated using western blotting. Results: The PI3K inhibitor, at different concentrations and times, increased the NIS mRNA level (1.30-6.17-fold, P < 0.0001). If the NIS mRNA level in LY294002-treated CD133-positive CSCs was increased more than 2-fold, the NIS protein content was detectable. Conclusions: CD133-positive CSCs isolated from ATC cell lines expressed NIS mRNA and protein after PI3K inhibition. Our findings suggest that molecularly targeted CSC therapy may improve the treatment efficacy of aggressive cancers like ATC.

Keywords

Main Subjects