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 125I. 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.