Abstract：
Polybrominated diphenyl ethers (PBDEs) have been reported to possess endocrine-disrupting and tumour-promoting activity. However, the effects of long-term exposure to decabromodiphenyl ether (BDE209) on thyroid tumourigenesis of papillary thyroid carcinoma (PTC) and the underlying mechanisms remain poorly defined. In this study, functional assays in vitro and mouse models in vivo were used to evaluate the toxic effects of long-term exposure to environmental concentrations of BDE209 on the pathogenesis and progression of PTC. MTS, EdU and colony-forming assays confirmed the chronic toxicity of BDE209 on the proliferation of human normal follicular epithelial cell line (Nthy-ori 3-1) and PTC-derived cell lines (TPC-1 and BCPAP). Wound and Transwell assays showed that BDE209 exacerbated the aggressiveness of PTC cells. BDE209 significantly promoted cell proliferation during the S and G2/M phases of the cell cycle. Mechanistically, BDE209 altered the thyroid system by acting as a competitive inhibitor of thyroid receptor beta (TRß) expression and function, which was further proven by public databases and RNA-seq bioinformation analysis. Taken together, these results demonstrated that BDE209 has chronic toxicity and potential tumourigenic effects on the thyroid by inhibiting TRß.
摘要：
据报道，多溴联苯醚（PBDEs）具有内分泌干扰和促进肿瘤的活性。然而,长期暴露于十溴二苯醚(BDE209)对甲状腺乳头状癌(PTC)的甲状腺肿瘤发生的影响及其潜在机制仍不明确。在这项研究中,使用体外功能测定和体内小鼠模型来评估长期暴露于环境浓度的BDE209对PTC的发病机理和进展的毒性作用。MTS,EdU和集落形成试验证实了BDE209对人正常滤泡上皮细胞系(Nthy-ori3-1)和PTC来源细胞系(TPC-1和BCPAP)增殖的慢性毒性。伤口和Transwell测定显示BDE209加剧了PTC细胞的侵袭性。BDE209在细胞周期的S和G2/M期显著促进细胞增殖。机械上,BDE209作为甲状腺受体β（TRβ）表达和功能的竞争性抑制剂，改变了甲状腺系统，公共数据库和RNA-seq生物信息分析进一步证明了这一点。一起来看,这些结果表明,BDE209通过抑制TRβ对甲状腺具有慢性毒性和潜在的致瘤作用.
