ATRA increases iodine uptake and inhibits the proliferation and invasiveness of human anaplastic thyroid carcinoma SW1736 cells: Involvement of β-catenin phosphorylation inhibition

All-trans-retinoic acid (ATRA) can enhance iodine uptake capability of thyroid tumors, but the mechanisms remain poorly understood. The aim of the present study was to investigate the effects of ATRA on isotope susceptibility, proliferation and invasion of anaplastic thyroid carcinoma (ATC) and potential mechanisms. SW1736 cells were treated with 1 µmol/l ATRA or 1% ethanol for 5 days. A cell line stably expressing β-catenin-shRNA was established. An iodine uptake assay was performed using 125 I. Proliferation and invasiveness were tested using MTT and Transwell assays, respectively. Western blotting was used to assess the expression of β-catenin, glycogen synthase kinase-3β (GSK-3β), sodium/iodine symporter (NIS) and proteins involved in epithelial-mesenchymal transition. Cells pretreated with ATRA were injected subcutaneously into SCID mice. Mice were intraperitoneally injected with ¹³¹I once on the first day of treatment, and tumor growth was then assessed. After 35 days of ¹³¹I treatment, ATRA-pretreated tumor volume and weight were decreased compared with the ¹³¹I alone group (163.32±19.57 vs. 332.06±21.37 mm³; 0.35±0.14 vs. 0.67±0.23 g, both P<0.05). Similar results were observed in the β-catenin shRNA-pretreated tumors. ATRA also increased the uptake of iodine by SW1736 cells (P<0.01), and similar results were observed in β-catenin shRNA cells. ATRA treatment decreased the cell proliferation and invasion compared with control cells (all P<0.05), similar to β-catenin shRNA. ATRA treatment decreased the expression of phosphorylated (p-)β-catenin, p-GSK-3β, vimentin, and fibronectin, and increased the expression of NIS and E-cadherin, compared with the control. ATRA increased the iodine uptake and inhibited the proliferation and invasion of SW1736 cells, involving β-catenin phosphorylation. In conclusion, ATRA could be used to improve the isotope sensitivity of ATC.