Effect of Sunitinib on Growth and Function of FRTL-5 Thyroid Cells
- 1 June 2008
- journal article
- research article
- Published by Mary Ann Liebert Inc in Thyroid®
- Vol. 18 (6), 631-635
- https://doi.org/10.1089/thy.2007.0336
Abstract
Background: Sunitinib, a multitargeted vascular endothelial growth factor and receptor tyrosine kinase inhibitor, causes hypothyroidism in patients who take it for treatment of cancer. Although the pathophysiologic mechanism of the hypothyroidism is unclear, it has been claimed that it is due to inhibition of iodide uptake. Methods: To evaluate the pathologic mechanism of induction of the hypothyroidism, we studied the effect of sunitinib on FRTL-5 rat thyroid cells. We measured the effect of sunitinib on cell growth, 125I-iodide uptake and efflux, TSH receptor (TSH-R), and sodium-iodide symporter (NIS) message. Results: At 48 hours, sunitinib caused a dose-related inhibition of growth with LC50 of 14.6 μM, but there was no apparent inhibition of growth at 24 hours at concentrations of 0.1–25 μM. Preincubation with sunitinib did not impair the response to TSH, indicating that it did not affect the TSH-R. Incubation with sunitinib for 24 hours caused a dose-related increase of 125I-iodide uptake and did not reduce iodide efflux or NIS mRNA expression. Conclusion: The data indicate that sunitinib is unlikely to cause hypothyroidism by inhibition of iodide uptake.Keywords
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