All-trans retinoic acid improves the iodine uptake of thyroid cancer cells. - GreenMedInfo Summary
[All-trans retinoic acid improves iodine uptake of thyroid cancer cells via repressing transcriptional activity ofβ-catenin].
Zhonghua Yi Xue Za Zhi. 2016 Feb 23 ;96(7):553-558. PMID: 26902198
Objective: To determine whether all-trans retinoic acid (ATRA) could improve iodine uptake via repressing transcriptional activity ofβ-catenin in thyroid cancer cells. Methods: Three kinds of treatment models were firstly established with alcohol, ATRA, and transfection of β-catenin shRNA in undifferentiated human thyroid cancer cell line-SW1736.Then the expressions of sodium iodide symporter (NIS), β-catenin and its regulating factors, epithelial-mensechymal transition (EMT)-phenotype, invasion and metastasis associated proteins were further measured in above three cell models.After that, the influence of ATRA on the functional expression of NIS, iodine uptake potency, tumor growth curve and treatment effect inducing byradioactive iodine was comparatively analyzed in vitro and in vivo trials. Results: After treated with ATRA, transcriptional activity of β-catenin decreased by downregulating phosphorylation of β-catenin Ser45、Y654 and GSK-3β Ser9.Additionally, ATRA effectively upregulated the protein level ofNIS, and reversed EMT phenotype in alcohol treated cells, with absence in epithelial expression of E-cadherin and cytokeratin 18, as well as abnormal expression of Vimentin, urinary plasminogen activator (uPA), uPAR and Fibronectin.Compared with alcohol-treated group, both in vitro proliferation and invasion potential of ATRA treated cells markedly decreased (all P<0.05), and iodine uptake in vitro increased about 3.5-folds (P=0.007). In ATRA-treated animal model, tumor growth potential and tumor mass were significantly inhibited by radio-iodine ((131)I) treatment (all P<0.05). Conclusions: ATRA can increase functional expression of NIS via downregulating transcriptional activity ofβ-catenin and promote isotope sensitivity to radio-iodine in human undifferentiated thyroid cancer.