Shang Hongxia, Zhao Junyu, Yao Jinming, Wang Huanjun, Dong Jianjun, Liao Lin
Department of Endocrinology and Metabology, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Ji-nan, China.
Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University, Ji-nan, China.
Front Oncol. 2020 Mar 31;10:404. doi: 10.3389/fonc.2020.00404. eCollection 2020.
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 and , 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.
奈韦拉平已被证明在诱导多种肿瘤细胞重新分化和抑制肿瘤生长方面有效。本研究旨在探讨奈韦拉平对放射性碘治疗难治性去分化甲状腺癌（DeTC）的治疗潜力及其潜在机制。结果表明，奈韦拉平显著抑制去分化甲状腺癌细胞（WRO 82-1和dFTC-133）的增殖，并增加甲状腺分化相关基因、促甲状腺激素受体（TSHR）、钠/碘同向转运体（NIS）、甲状腺过氧化物酶（TPO）和转录因子配对盒8（PAX8）的表达。此外，奈韦拉平在体内和体外均显著增强放射性碘摄取，并抑制异种移植肿瘤的生长。奈韦拉平可能通过激活TSHR/cAMP/CREB/PAX8信号通路提高放射性碘敏感性。本研究表明，奈韦拉平有可能用于提高去分化甲状腺癌患者的放射性碘治疗效果。
