Increased iodine uptake in thyroid carcinoma after treatment with sodium butyrate and decitabine (5-Aza-dC).

ABSTRACT

OBJECTIVE: To determine if epigenetic-modifying drugs can increase iodine uptake in thyroid carcinoma cell lines. STUDY DESIGN: Human thyroid carcinoma cell lines were tested for iodine uptake before and after treatment with epigenetic-modifying agents. RESULTS: Thyroid carcinoma cell lines DRO and 2-7 had high levels of DNA methylation (74% and 80%) compared with normal thyroid tissue (6%) (P < 0.05). This finding correlated with low levels of sodium iodide symporter (NIS) expression in the untreated thyroid carcinoma cell line. Combination treatment with the epigenetic-modifying agents 5-aza-2'-deoxycytidine and sodium butyrate resulted in increases in NIS messenger RNA levels, global histone acetylation, and 9- and 8-fold increases in I(125) uptake for the DRO and 2-7 cells, respectively. CONCLUSIONS: Epigenetic-modifier drugs represent a novel adjuvant treatment for those patients with radioablation-resistant thyroid cancer. SIGNIFICANCE: Epigenetic-modifying agents show potential for treatment of radioablation-resistant thyroid cancer.