Selective thyroid hormone receptor beta agonist, GC-1, is capable to reduce growth of colorectal tumor in syngeneic mouse models. (3rd September 2022)

• Record Type: Journal Article
• Authors: Pourvali, Katayoun; Shimi, Ghazaleh; Ghorbani, Arman; Shakery, Azam; Shirazi, Farshad Hosseini; Zand, Hamid
• Is Part Of: Journal of receptor and signal transduction research. Volume 42:Number 5(2022)
• Page Start: 495
• Page End: 502
• Publication Date: 2022-09-03
• Subjects: Thyroid hormone receptor beta -- GC-1 -- tumor growth -- tumor suppressor -- colorectal cancer; Cell receptors -- Periodicals; Cellular signal transduction -- Periodicals; 571.6
• DOI: 10.1080/10799893.2022.2032748
• Languages: English
• ISSNs: 1079-9893

Abstract

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 [ 18 F] 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 18 FDG 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.