Abstract
Nevirapine has been proved to be effective in inducing re-differentiation and suppressing tumor growth in several tumor cells. This study aims to investigate the therapeutic potential of nevirapine in dedifferentiated thyroid cancer (DeTC), which refractory to radioiodine treatment and the underlying mechanisms. The results indicated that nevirapine significantly inhibited the proliferation and increased the expressions of thyroid differentiation-related genes, thyroid stimulating hormone receptor (TSHR), sodium/iodide symporter (NIS), thyroid peroxidase (TPO), and transcriptional factor paired box 8 (PAX8) in dedifferentiated thyroid cancer cells (WRO 82-1 and dFTC-133). Furthermore, nevirapine also enhanced radioiodide uptake significantly both in vitro and in vivo, and inhibited the growth of xenograft tumors. Nevirapine might improve radioiodine sensitivity via the activation of TSHR/cAMP/CREB/PAX8 signaling pathway. This study demonstrates that nevirapine could be potentially used to improve radioiodine therapeutic efficacy in dedifferentiated thyroid cancer patients.
Highlights
Thyroid cancer, the most common endocrine malignancy, has increased substantially worldwide [1]
We previously showed that nevirapine upregulated thyroid stimulating hormone receptor (TSHR) mRNA in anaplastic thyroid carcinoma cells, which could increase the expression of cAMP [37, 38]. cAMP-response element binding protein (CREB) is a key mediator of TSH in thyroid cells, which can mediate thyroid cells function, such as, thyroid hormone production and iodide uptake [38]
The dedifferentiated thyroid carcinoma (DeTC) may occur in recurrence or metastasis of previously treated Well-differentiated thyroid cancer (WDTC), which loses a number of markers related to thyroid cell differentiation
Summary
The most common endocrine malignancy, has increased substantially worldwide [1]. Well-differentiated thyroid cancer (WDTC) is a generally slow-growing tumor with a good prognosis, its 20-year overall survival rate is more than 90% via conventional therapy [3, 4]. Thyroidectomy and thyroid hormone suppression therapy with or without thyroid cancer remnant and metastasis ablation by radioiodine treatment are widely accepted as routine therapies for WDTC [2]. During these treatment, around 30% of WDTC may progress to dedifferentiated thyroid cancer (DeTC), Nevirapine Increases Radioiodide Uptake a state occupying an intermediate position in both morphology and behavior between WDTC and anaplastic thyroid cancer (ATC) [5, 6]. 10-year survival rate of DeTC declines to ∼15–20% [7, 8]
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