2. Academic Validation
  3. Decabromodiphenyl ether exposure reduces dabrafenib sensitivity of papillary thyroid carcinoma harboring BRAFV600E mutation through the EGFR-CRAF-MAPK pathway: An in vitro study

Decabromodiphenyl ether exposure reduces dabrafenib sensitivity of papillary thyroid carcinoma harboring BRAFV600E mutation through the EGFR-CRAF-MAPK pathway: An in vitro study

  • Toxicology. 2024 May:504:153807. doi: 10.1016/j.tox.2024.153807.
Xinpei Wang 1,  Xiujie Cui 2,  Yi Wang 3,  Qianqian Wang 4,  Feifei Sun 5,  Zhiyan Liu 6
Affiliations

Affiliations

  • 1 Department of Pathology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600# Yishan Rd, Shanghai 200233, People's Republic of China; Shanghai Comprehensive Oncology Center of Bone and Soft Tissue, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600# Yishan Rd, Shanghai, 200233, People's Republic of China. Electronic address: [email protected].
  • 2 The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, People's Republic of China. Electronic address: [email protected].
  • 3 Department of Pathology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600# Yishan Rd, Shanghai 200233, People's Republic of China; Shanghai Comprehensive Oncology Center of Bone and Soft Tissue, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600# Yishan Rd, Shanghai, 200233, People's Republic of China. Electronic address: [email protected].
  • 4 Department of Pathology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600# Yishan Rd, Shanghai 200233, People's Republic of China; Shanghai Comprehensive Oncology Center of Bone and Soft Tissue, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600# Yishan Rd, Shanghai, 200233, People's Republic of China; Jinzhou Medical University Graduate Training Base (Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine), Jinzhou 121001, People's Republic of China. Electronic address: [email protected].
  • 5 Department of Pathology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, People's Republic of China. Electronic address: [email protected].
  • 6 Department of Pathology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600# Yishan Rd, Shanghai 200233, People's Republic of China; Shanghai Comprehensive Oncology Center of Bone and Soft Tissue, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600# Yishan Rd, Shanghai, 200233, People's Republic of China. Electronic address: [email protected].
PMID: 38641160 DOI: 10.1016/j.tox.2024.153807
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.

Keywords

BDE209; BRAF(V600E) mutation; Dabrafenib; MAPK; papillary thyroid carcinoma.

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