Therapeutic Potential of Sodium Selenite Application for Promoting Radioactive Iodine Avidity in Papillary Thyroid Cancer

Objective: Radioactive iodine therapy is a mainstay for recurrent and metastatic differentiated thyroid cancer. However, a substantial portion of differentiated thyroid cancer patients exhibits dedifferentiation status with a lack of sodium iodide symporter functionality and expression, as well as downregulated thyroid-specific proteins and transcription factors. Eventually, this status is connected to the failure of radioactive iodine therapy with an overall poor prognosis. Selenium, an essential trace element, has antitumor, antioxidant, immunomodulatory, and antiviral activities and is required for thyroid hormone synthesis and metabolism, and it was reported that sodium selenite induces radioactive iodine uptake in thyroid tissue in rats. However, the relationship between sodium selenite and differentiation markers in differentiated thyroid cancer remains unclear. Methods: We investigated whether sodium selenite enhances radioactive iodine avidity and reinforces ¹³¹I therapeutic effects in papillary thyroid cancer cells. We also analyzed changes in selected signaling pathways and factors induced by sodium selenite treatment. Results: Sodium iodide symporter, thyroid-specific proteins, and transcription factors were upregulated by sodium selenite, increasing radioactive iodine avidity and radioactive iodine-mediated cytotoxicity in papillary thyroid cancer cells. Sodium selenite downregulated the MAPK, PI3K–AKT, and GSK-3β/β-catenin signaling pathways. Conclusion: Sodium selenite may serve as a promising adjunct to enhance radioactive iodine avidity in papillary thyroid cancer cells.