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Effect of sunitinib on growth and function of FRTL-5 thyroid cells
Andrew K Salem1, Mike S Fenton, Kenneth M Marion
1Endocrine Research Laboratory, Endocrinology and Diabetes Division, Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, California 90073, USA.
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, (125)I-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 LC(50) of 14.6 muM, but there was no apparent inhibition of growth at 24 hours at concentrations of 0.1-25 microM. 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 (125)I-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.
Insights
Sunitinib treatment for cancer can cause hypothyroidism. This study found sunitinib does not inhibit iodide uptake in rat thyroid cells, suggesting it is unlikely to cause hypothyroidism through this mechanism.
Area of Science:
- Endocrinology
- Oncology
- Pharmacology
Background:
- Sunitinib, a tyrosine kinase inhibitor, is used for cancer treatment.
- Sunitinib is known to cause hypothyroidism, but the mechanism remains unclear.
- A proposed mechanism involves the inhibition of iodide uptake.
Purpose of the Study:
- To investigate the mechanism by which sunitinib induces hypothyroidism.
- To evaluate the effect of sunitinib on rat thyroid cells (FRTL-5).
Main Methods:
- Assessed sunitinib's impact on FRTL-5 cell growth, iodide uptake and efflux.
- Measured TSH receptor (TSH-R) and sodium-iodide symporter (NIS) gene expression.
Main Results:
- Sunitinib inhibited cell growth at 48 hours (LC50 = 14.6 muM) but not at 24 hours.
- Sunitinib did not affect TSH receptor response.
- Sunitinib increased iodide uptake and did not reduce iodide efflux or NIS mRNA levels.
Conclusions:
- Sunitinib is unlikely to cause hypothyroidism by inhibiting iodide uptake.
- The mechanism of sunitinib-induced hypothyroidism requires further investigation.
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