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

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Published on Friday, 19 January 2018

Abstract

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.

 

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See also:

- All-Trans-Retinoic Acid (ATRA - analogues and/or derivatives);

- The Di Bella Method (A Fixed Part - All-Trans Retinoic Acid);

- Solution of retinoids in vitamin E in the Di Bella Method biological multitherapy;

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- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;

- The Di Bella Method Increases by the 30% the survival rate for Pancreas tumors and for this reason should be proposed as first line therapy for this type of cancer;

- Chronic Lymphocytic Leukemia: Long-Lasting Remission with Combination of Cyclophosphamide, Somatostatin, Bromocriptine, Retinoids, Melatonin, and ACTH;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma.