Propranolol sensitizes thyroid cancer cells to cytotoxic effect of vemurafenib

Oncol Rep. 2016 Sep;36(3):1576-84. doi: 10.3892/or.2016.4918. Epub 2016 Jul 7.


Treatment options for advanced metastatic or progressive thyroid cancers are limited. Although targeted therapy specifically inhibiting intracellular kinase signaling pathways has markedly changed the therapeutic landscape, side-effects and resistance of single agent targeted therapy often leads to termination of the treatment. The objective of the present study was to identify the antitumor property of the non-selective β-adrenergic receptor antagonist propranolol for thyroid cancers. Human thyroid cancer cell lines 8505C, K1, BCPAP and BHP27 were used in the present study. Broad β-blocker propranolol and β2-specific antagonist ICI118551, but not β1-specific antagonist atenolol, inhibited the growth of 8505C and K1 cells. Propranolol treatment inhibited growth and induced apoptosis of 8505C cells in vitro and in vivo, which are closely associated with decreased expressions of cyclin D1 and anti-apoptotic Bcl-2. Expression of hexokinase 2 (HK2) and glucose transporter 1 (GLUT1) also decreased following propranolol intervention. 18F-FDG PET/CT imaging of the 8505C xenografts validated shrinkage of the tumors in the propranolol-treated group when compared to the phosphate‑buffered saline treated group. Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib. Our present results suggest that propranolol has potential activity against thyroid cancers and investigation of the combination with targeted molecular therapy for progressive thyroid cancers could be beneficial.

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Indoles / pharmacology*
  • Mice
  • Mice, Nude
  • Propranolol / pharmacology*
  • Sulfonamides / pharmacology*
  • Thyroid Neoplasms / pathology*
  • Vemurafenib
  • Xenograft Model Antitumor Assays


  • Adrenergic beta-Antagonists
  • Indoles
  • Sulfonamides
  • Vemurafenib
  • Propranolol