The relationship between the radioresistance of anaplastic thyroid cancer and the induction of epithelial- mesenchymal transition
10.3760/cma.j.cn113030-20240925-00372
- VernacularTitle:上皮间充质转化在未分化甲状腺癌细胞放射抵抗中的作用
- Author:
Mingyue LI
1
;
Chengzhi LIU
;
Difan WANG
;
Hongying YANG
;
Shang CAI
;
Ye TIAN
;
Siyuan LI
;
Ruiqiu ZHU
Author Information
1. 苏州大学附属第二医院放疗科，苏州 215004
- Publication Type:Journal Article
- Keywords:
Thyroid neoplasms, anaplastic;
Epithelial mesenchymal transition;
Radioresistance
- From:
Chinese Journal of Radiation Oncology
2025;34(6):607-616
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the relationship between the radioresistance of anaplastic thyroid cancer (ATC) and the induction of epithelial-mesenchymal transition (EMT).Methods:Firstly, the radiotherapy sensitivity of differentiated thyroid cancer cells (TPC-1, FTC-133) and ATC cells (CAL-62, 8305C), and the protein levels of E-cadherin, N-cadherin and vimentin proteins after 6 Gy irradiation were detected. The changes in transcriptional levels before and after 4 Gy X-ray radiation of ATC cells were analyzed using mRNA sequencing. Then, the ATC radio-resistant cell models were constructed and validated, and the cell line with the highest radio-resistance was selected for subsequent experiments. Radio-resistant cells were classified into the control group (no treatment), EMT-inhibitor group (EMT-inhibitor-1 pre-treatment), Vactosertib group [transforming growth factor-β(TGF-β) inhibitor Vactosertib pre-treatment), and si-Snail group (knockdown of Snail gene by siRNA transfection), respectively. The expression level of EMT related proteins and TGF-β/Smad signaling pathway related proteins, the cloning efficiency, and the phosphorylated-histone H2A family member X (γH2AX) positive cells rate in the treatment groups and the control group were detected by Western blotting, clone formation assay, immunofluorescence, respectively, reflecting the changes in EMT level and DNA repair ability. Comparison between two groups was performed by Dunnett t-test. Comparison among multiple groups was conducted by one-way ANOVA. Results:The radiosensitivity of ATC cells were lower than that of differentiated thyroid cancer cells. After irradiation, the expression level of E-cadherin was low, those of N-cadherin and vimentin were high, EMT level was increased, and the expression levels of TGF-β/Smad signaling pathway-associated proteins were up-regulated in ATC cells. After use of EMT inhibitor, Vactosertib and Snail knockdown, the expression levels of EMT-associated proteins were down-regulated, cell survival fraction was declined, γH2AX positive cell rate was increased, DNA damage repair ability was weakened and the radiosensitivity was enhanced in radiotherapy-resistant ATC strains. Conclusions:The level of radiotherapy resistance in ATC cells is positively correlated with the EMT level, and the mechanism of radiotherapy resistance is related to the activation of the TGF-β/Smad/Snail pathway after irradiation.
