Abstract
Objective
The effect of thyroid hormone (TH) on cancers was proposed more than 100 years ago; however, conclusions are conflicting. THs are precisely regulated at tissue and cellular levels. It seems that this regulation is altered in cancers. Thyroid hormone receptor beta (TRβ) has anti-proliferative and tumor-suppressive effects in many cancer cells. Therefore, we decided to investigate thyroid hormone receptor beta (THRB) expression and activation by the selective agonist, GC-1, on tumor growth in a syngeneic mouse model of colorectal cancer (CRC) and colon cell lines.
Methods
In vitro cell viability assay using MTT analysis, cell cycle analysis by PI staining, and FACS analysis were performed. In vivo tumor growth measurements were carried out by caliper and [18F] Fluoro-2-deoxy-2-D-glucose (FDG) – PET imaging. Gene expressions were determined using quantitative-PCR.
Results
Some concentrations of GC-1 had a marked negative effect on the cell viability of colorectal cell lines. Cell cycle analysis showed that the anti-proliferative effect of GC-1 may not result from cell cycle arrest or apoptosis. Tumor growth analysis in mice harboring colorectal tumor showed that GC-1 treatment for 8 d profoundly inhibited tumor growth and 18FDG uptake. THRB expression was decreased in mice tumor; however, it was upregulated following GC-1 administration.
Conclusions
Our results showed that specific activation of TRβ by GC-1 had negative effect on tumor growth and restored its gene expression in tumors of CRC mice model.
Correction Statement
This article has been corrected with minor changes. These changes do not impact the academic content of the article.
Acknowledgments
The present authors would like to express their gratitude to colleagues of the Laboratory of Cellular and Molecular Nutrition Research, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Science, and Food Technology Shahid Beheshti University of Medical Sciences, Tehran, Iran for supporting this study.
Ethics approval
The ethics committee at the National Nutrition and Food Technology Research Institute of Shahid Beheshti University of Medical Sciences approved the study protocol (code of ethics committee: IR.SBMU.RETECH.REC.1400.296).
Disclosure statement
The authors report there are no competing interests to declare.
Data availability statement
The analyzed data sets generated during the study are available from the corresponding author on reasonable request.