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Spontaneous Murine Model of Anaplastic Thyroid Cancer
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Spontaneous Murine Model of Anaplastic Thyroid Cancer

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Dual Inhibition of BRAF-MAPK and STAT3 Signaling Pathways in Resveratrol-Suppressed Anaplastic Thyroid Cancer Cells

Meng-Di Lu1, Hong Li2, Jun-Hua Nie1

  • 1School of Medicine, South China University of Technology, Guangzhou 510006, China.

International Journal of Molecular Sciences
|November 26, 2022
PubMed

Insights

Resveratrol effectively inhibits anaplastic thyroid cancer (ATC) cell growth by targeting both BRAF-MAPK and STAT3 signaling pathways. This natural compound shows promise as a dual inhibitor for treating ATCs harboring BRAF mutations.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Anaplastic thyroid cancer (ATC) is a highly lethal malignancy with limited treatment options.
  • BRAF mutations, particularly BRAFV600E, are prevalent in ATCs and activate the MAPK signaling pathway, presenting a therapeutic target.
  • The effect of resveratrol on BRAF-MAPK signaling in ATC remains largely unexplored.

Purpose of the Study:

  • To investigate the impact of resveratrol on BRAF-MAPK and STAT3 signaling pathways in different ATC cell lines.
  • To evaluate the efficacy of resveratrol as a potential therapeutic agent for BRAF-mutated ATCs.

Main Methods:

  • Utilized RT-PCR and Sanger sequencing to identify BRAF mutations (MKRN1-BRAF fusion, BRAF V600E) in ATC cells.
  • Employed Western blotting and immunocytochemistry to assess MAPK pathway activation (pBRAF, pMEK, pERK).
  • Conducted cell viability (Calcein/PI), proliferation (EdU), and apoptosis (TUNEL) assays to compare resveratrol with standard chemotherapies and targeted agents.

Main Results:

  • Resveratrol demonstrated superior inhibition of cell growth in ATC cells with BRAF mutations (THJ-16T, THJ-21T) compared to docetaxel, doxorubicin, dabrafenib, and trametinib.
  • Resveratrol treatment led to decreased levels of MAPK pathway proteins and phosphorylated STAT3 (pSTAT3).
  • Resveratrol effectively suppressed STAT3 activation, which was previously enhanced by trametinib and dabrafenib.

Conclusions:

  • Resveratrol acts as a dual inhibitor of BRAF-MAPK and STAT3 signaling pathways.
  • Resveratrol exhibits significant potential as a therapeutic agent for anaplastic thyroid cancer with BRAF mutations.
Keywords:
BRAFV600E mutationMAPK signaling pathwayMKRN1-BRAF fusion mutationSTAT3 signaling pathwayanaplastic thyroid cancerresveratrol

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