Sobetirome

Cell lines

Anaplastic thyroid cancer cell lines

Preparation Method

Anaplastic thyroid cancer cell lines were cultured in RPMI 1640 growth medium with L-glutamine (300mg/L), sodium pyruvate, and nonessential amino acids (1%), supplemented with 10% fetal bovine serum and penicillin-streptomycin (200IU/L) at 37°C, 5% CO₂, and 100% humidity. Charcoal-stripped fetal bovine serum was used for hormone-induced gene expression analysis. Cell growth was measured by cell counting at discrete time points. Cells were seeded in 12-well plates, then treated with Sobetirome (10nM; 4 days). Cell viability was determined by a sulforhodamine B assay following the manufacturer’s protocol. Cell migration was determined by wound healing assay. Tumorspheres formed from ATC cells were used to assess self-renewal and sphere-forming efficiency. Cells were collected for Western blot and RT-PCR analyses.

Reaction Conditions

10nM; 4 days

Applications

Sobetirome reduces proliferation, slows migration, suppresses thyrosphere formation, increases NIS protein, and up-regulates thyroid-differentiation genes in anaplastic thyroid cancer cell lines.

Animal models

Female Wistar rats

Preparation Method

Female Wistar rats were obtained from our breeding colony and maintained under controlled conditions of light and temperature (12h darkness:12h light cycle at 25℃). All animals were kept in plastic cages, four per cage, and had free access to food (rat chow containing 1.4% Pi, 0.7% Ca and 4.5IU/g vitamin D) and water. At the age of 100 days and a weight of 210–220g, the animals were randomly divided into three groups (n=8 pergroup): (i) control, treated with saline; (ii) treated with T3 (6μg T3/100g body weight (BW) per day); (iii) treated with Sobetirome (3μg /100g BW per day). T3 was dissolved in 40mM NaOH, and Sobetirome was dissolved in DMSO to a concentration of 1mg/ml; either T3 or Sobetirome were then diluted in saline and administered i.p. every day for 6 weeks. BW was measured thrice a week (on Mondays, Wednesdays and Fridays). Body length (nose to base of the tail) was determined at the end of the experimental period. Once a week (weeks 1–6), the animals were individually maintained in metabolic cages for 24h for determination of food intake. Lean mass and fat mass were measured by dualenergy X-ray absorptiometry.

Dosage form

3μg/100g/day; i.p.; 6 weeks

Applications

Sobetirome reduced fat mass by 20% without increasing food intake or decreasing lean mass in adult female Wistar rats.

References:
[1] Gillis NE, Cozzens LM, Wilson ER, et al. TRβ Agonism Induces Tumor Suppression and Enhances Drug Efficacy in Anaplastic Thyroid Cancer in Female Mice. Endocrinology. 2023;164(10):bqad135.
[2] Villicev CM, Freitas FR, Aoki MS, et al. Thyroid hormone receptor beta-specific agonist GC-1 increases energy expenditure and prevents fat-mass accumulation in rats. J Endocrinol. 2007;193(1):21-29.