Abstract：
Decabromodiphenyl ether (BDE209) has been demonstrated to be associated with thyroid dysfunction and thyroid carcinoma risk as a widely used brominated flame retardants. Although dabrafenib has been confirmed to be a promising therapeutic agent for papillary thyroid carcinoma (PTC) harboring BRAFV600E mutation, the rapid acquired dabrafenib resistance has brought a great challenge to clinical improvement and the underpinning mechanisms remain poorly defined. By treating PTC-derived and normal follicular epithelial cell lines with BDE209, we assessed its impact on the MAPK pathway\'s activation and evaluated the resultant effects on cell viability and signaling pathways, utilizing methods such as Western blot, IF staining, and RNA-seq bioinformatic analysis. Our findings reveal that BDE209 exacerbates MAPK activation, undermining dabrafenib\'s inhibitory effects by triggering the EGFR pathway, thereby highlighting BDE209\'s potential to diminish the pharmacological efficacy of dabrafenib in treating BRAF-mutated PTC. This research underscores the importance of considering environmental factors like BDE209 exposure in the effective management of thyroid carcinoma treatment strategies.
摘要：
十溴二苯醚（BDE209）作为一种广泛使用的溴化阻燃剂，已被证明与甲状腺功能障碍和甲状腺癌风险有关。虽然dabrafenib已被证实是一种有前途的治疗甲状腺乳头状癌（PTC）有BRAFV600E突变的药物，快速获得的dabrafenib耐药性给临床改善带来了巨大挑战，基础机制仍然不明确。通过用BDE209处理PTC来源的和正常的滤泡上皮细胞系，我们评估了其对MAPK通路激活的影响，并评估了其对细胞活力和信号通路的影响。利用蛋白质印迹等方法，IF染色,和RNA-seq生物信息学分析。我们的研究结果表明，BDE209会加剧MAPK激活，通过触发EGFR通路破坏dabrafenib的抑制作用，从而突出了BDE209降低dabrafenib治疗BRAF突变PTC的药理功效的潜力。这项研究强调了在有效管理甲状腺癌治疗策略中考虑BDE209暴露等环境因素的重要性。
