Four human thyroid cancer cell lines (FTC-133, C643, 8505C and HTh74) were treated with 1,25(OH)2D3 or CD578, alone or in combination with paclitaxel or SAHA. Effects on cell growth and differentiation were evaluated.
Clear effects on growth arrest were observed in a clonogenic assay, and absolute cell counts demonstrated a 24–36 % reduction in all cell lines after 72 h treatment with 1,25(OH)2D3 (10−6 M) and a 60 % inhibition after 120 h in the most sensitive cell line HTh74. A similar growth inhibition was shown after treatment with a 1000-fold lower concentration of analog CD578. This growth arrest was explained by antiproliferative effects, further supported by an increased % of cells in the G0–G1 phase of the cell cycle and by a decreased transcription factor E2F1 mRNA expression. Combination treatments of 1,25(OH)2D3 or CD578 with paclitaxel or SAHA resulted in an additive and in some conditions a synergistic effect on the inhibition of proliferation. Redifferentiation analysis revealed only a modest increase in sodium iodide symporter and thyroglobulin mRNA expression after treatment with 1,25(OH)2D3, without additive effect after combination treatment. No effects were observed on TSH-receptor or thyroid peroxidase mRNA expression.
Our in vitro findings demonstrate that the superagonistic vitamin D analog CD578 holds promise as adjuvant antiproliferative therapy of anaplastic thyroid cancer, especially in combination with other drugs such as paclitaxel or SAHA.