Nevirapine Increases Sodium/Iodide Symporter-Mediated Radioiodide Uptake by Activation of TSHR/cAMP/CREB/PAX8 Signaling Pathway in Dedifferentiated Thyroid Cancer

Hongxia Shang; Junyu Zhao; Junyu Zhao; Jinming Yao; Huanjun Wang; Jianjun Dong; Lin Liao; Lin Liao

doi:10.3389/fonc.2020.00404

Frontiers in Oncology (Mar 2020)

Nevirapine Increases Sodium/Iodide Symporter-Mediated Radioiodide Uptake by Activation of TSHR/cAMP/CREB/PAX8 Signaling Pathway in Dedifferentiated Thyroid Cancer

Hongxia Shang,
Junyu Zhao,
Junyu Zhao,
Jinming Yao,
Huanjun Wang,
Jianjun Dong,
Lin Liao,
Lin Liao

Affiliations

Hongxia Shang: Department of Endocrinology and Metabology, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Ji-nan, China
Junyu Zhao: Department of Endocrinology and Metabology, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Ji-nan, China
Junyu Zhao: Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University, Ji-nan, China
Jinming Yao: Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University, Ji-nan, China
Huanjun Wang: Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University, Ji-nan, China
Jianjun Dong: Department of Endocrinology and Metabology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Ji-nan, China
Lin Liao: Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University, Ji-nan, China
Lin Liao: Department of Endocrinology and Metabology, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Ji-nan, China

DOI: https://doi.org/10.3389/fonc.2020.00404
Journal volume & issue: Vol. 10

Abstract

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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.

Published in Frontiers in Oncology

ISSN: 2234-943X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.frontiersin.org/journals/oncology/

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