Abstract
1337
Objectives Treatment options for advanced metastatic or progressive thyroid cancers are limited. Although targeted therapy specifically inhibiting intracellular kinase signaling pathways has dramatically changed the therapeutic landscape, side effects and resistance of single agent targeted therapy often leads to termination of the treatment. The objective of this study was to identify the anti-tumor property of the nonselective β-adrenergic receptor antagonist propranolol for thyroid cancers.
Methods Human thyroid cancer cell lines 8505C, K1, BCPAP and BHP27 were used to investigate the potential anti-thyroid cancer property of propranolol. Cell viability, cell cycle, apoptosis, western blotting, nuclear fragmentation and colony formation were assessed following propranolol, atenolol, ICI118551 and vemurafenib intervention. And then 5-week-old nude mice were injected with 2x106 8505C cells in RPMI 1640 subcutaneously in the left flank and 18F-FDG-PET/CT was performed to evaluate the inhibitory effect of propranolol on 8505C xenografts.
Results Broad beta-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. Expressions 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 PBS-treated group. Consistently immunohistochemistry of the tumor specimens in the treatment group confirmed the decreased expressions of Bcl-2 and cyclin D1. Finally we found that the combination of vemurafenib and propranolol amplified the cytotoxicity of vemurafenib and may provide clinical benefits with minimal side effects to BRAFV600E mutant advanced thyroid cancer patients in clinical trials.
Conclusions Our present results suggest that propranolol has potential activity against thyroid cancers and can be investigated in combination with targeted molecular therapy for progressive thyroid cancers in the future.
In this issue
Jump to section
Related Articles
Cited By...
- No citing articles found.