Sinomenine Hydrochloride Promotes TSHR-Dependent Redifferentiation in Papillary Thyroid Cancer

Radioactive iodine (RAI) plays an important role in the diagnosis and treatment of papillary thyroid cancer (PTC). The curative effects of RAI therapy are not only related to radiosensitivity but also closely related to the accumulation of radionuclides in the lesion in PTC. Sinomenine hydrochloride...

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Main Authors: Jing Zhang, Aomei Zhao, Xi Jia, Xinru Li, Yiqian Liang, Yan Liu, Xin Xie, Xijie Qu, Qi Wang, Yuemin Zhang, Rui Gao, Yan Yu, Aimin Yang
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/18/10709
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author Jing Zhang
Aomei Zhao
Xi Jia
Xinru Li
Yiqian Liang
Yan Liu
Xin Xie
Xijie Qu
Qi Wang
Yuemin Zhang
Rui Gao
Yan Yu
Aimin Yang
author_facet Jing Zhang
Aomei Zhao
Xi Jia
Xinru Li
Yiqian Liang
Yan Liu
Xin Xie
Xijie Qu
Qi Wang
Yuemin Zhang
Rui Gao
Yan Yu
Aimin Yang
author_sort Jing Zhang
collection DOAJ
description Radioactive iodine (RAI) plays an important role in the diagnosis and treatment of papillary thyroid cancer (PTC). The curative effects of RAI therapy are not only related to radiosensitivity but also closely related to the accumulation of radionuclides in the lesion in PTC. Sinomenine hydrochloride (SH) can suppress tumor growth and increase radiosensitivity in several tumor cells, including PTC. The aim of this research was to investigate the therapeutic potential of SH on PTC cell redifferentiation. In this study, we treated BCPAP and TPC-1 cells with SH and tested the expression of thyroid differentiation-related genes. RAI uptake caused by SH-pretreatment was also evaluated. The results indicate that 4 mM SH significantly inhibited proliferation and increased the expression of the thyroid iodine-handling gene compared with the control group (<i>p</i> < 0.005), including the sodium/iodide symporter (NIS). Furthermore, SH also upregulated the membrane localization of NIS and RAI uptake. We further verified that upregulation of NIS was associated with the activation of the thyroid-stimulating hormone receptor (TSHR)/cyclic adenosine monophosphate (cAMP) signaling pathway. In conclusion, SH can inhibit proliferation, induce apoptosis, promote redifferentiation, and then increase the efficacy of RAI therapy in PTC cells. Thus, our results suggest that SH could be useful as an adjuvant therapy in combination with RAI therapy in PTC.
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spelling doaj.art-b23799a19b39484a9cfbc7dd1cdce3fc2023-11-23T16:46:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181070910.3390/ijms231810709Sinomenine Hydrochloride Promotes TSHR-Dependent Redifferentiation in Papillary Thyroid CancerJing Zhang0Aomei Zhao1Xi Jia2Xinru Li3Yiqian Liang4Yan Liu5Xin Xie6Xijie Qu7Qi Wang8Yuemin Zhang9Rui Gao10Yan Yu11Aimin Yang12Department of Nuclear Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Nuclear Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Nuclear Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Nuclear Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Nuclear Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Nuclear Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Nuclear Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Nuclear Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Nuclear Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Nuclear Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Nuclear Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Public Health, Health Science Center of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Nuclear Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaRadioactive iodine (RAI) plays an important role in the diagnosis and treatment of papillary thyroid cancer (PTC). The curative effects of RAI therapy are not only related to radiosensitivity but also closely related to the accumulation of radionuclides in the lesion in PTC. Sinomenine hydrochloride (SH) can suppress tumor growth and increase radiosensitivity in several tumor cells, including PTC. The aim of this research was to investigate the therapeutic potential of SH on PTC cell redifferentiation. In this study, we treated BCPAP and TPC-1 cells with SH and tested the expression of thyroid differentiation-related genes. RAI uptake caused by SH-pretreatment was also evaluated. The results indicate that 4 mM SH significantly inhibited proliferation and increased the expression of the thyroid iodine-handling gene compared with the control group (<i>p</i> < 0.005), including the sodium/iodide symporter (NIS). Furthermore, SH also upregulated the membrane localization of NIS and RAI uptake. We further verified that upregulation of NIS was associated with the activation of the thyroid-stimulating hormone receptor (TSHR)/cyclic adenosine monophosphate (cAMP) signaling pathway. In conclusion, SH can inhibit proliferation, induce apoptosis, promote redifferentiation, and then increase the efficacy of RAI therapy in PTC cells. Thus, our results suggest that SH could be useful as an adjuvant therapy in combination with RAI therapy in PTC.https://www.mdpi.com/1422-0067/23/18/10709sinomenine hydrochlorideredifferentiationsodium/iodide symporterradioactive iodine uptakepapillary thyroid cancer
spellingShingle Jing Zhang
Aomei Zhao
Xi Jia
Xinru Li
Yiqian Liang
Yan Liu
Xin Xie
Xijie Qu
Qi Wang
Yuemin Zhang
Rui Gao
Yan Yu
Aimin Yang
Sinomenine Hydrochloride Promotes TSHR-Dependent Redifferentiation in Papillary Thyroid Cancer
International Journal of Molecular Sciences
sinomenine hydrochloride
redifferentiation
sodium/iodide symporter
radioactive iodine uptake
papillary thyroid cancer
title Sinomenine Hydrochloride Promotes TSHR-Dependent Redifferentiation in Papillary Thyroid Cancer
title_full Sinomenine Hydrochloride Promotes TSHR-Dependent Redifferentiation in Papillary Thyroid Cancer
title_fullStr Sinomenine Hydrochloride Promotes TSHR-Dependent Redifferentiation in Papillary Thyroid Cancer
title_full_unstemmed Sinomenine Hydrochloride Promotes TSHR-Dependent Redifferentiation in Papillary Thyroid Cancer
title_short Sinomenine Hydrochloride Promotes TSHR-Dependent Redifferentiation in Papillary Thyroid Cancer
title_sort sinomenine hydrochloride promotes tshr dependent redifferentiation in papillary thyroid cancer
topic sinomenine hydrochloride
redifferentiation
sodium/iodide symporter
radioactive iodine uptake
papillary thyroid cancer
url https://www.mdpi.com/1422-0067/23/18/10709
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