J Cancer 2020; 11(23):6883-6891. doi:10.7150/jca.48180 This issue

Research Paper

Biological implications of PTEN upregulation and altered sodium/iodide symporter intracellular distribution in resveratrol-suppressed anaplastic thyroid cancer cells

Le Xiong1, Jun-Hua Nie1, Xiao-Min Lin1, Jian-Bin Wu3, Zhen Chen2, Bo Xu2, Jia Liu1,2✉

1. South China University of Technology School of Medicine, Guangzhou 510006, China.
2. Department of Thyroid Surgery, Guangzhou First People's Hospital, South China University of Technology School of Medicine, Guangzhou 510180, China.
3. Department of Oncology, First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510405, P.R. China.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Xiong L, Nie JH, Lin XM, Wu JB, Chen Z, Xu B, Liu J. Biological implications of PTEN upregulation and altered sodium/iodide symporter intracellular distribution in resveratrol-suppressed anaplastic thyroid cancer cells. J Cancer 2020; 11(23):6883-6891. doi:10.7150/jca.48180. Available from https://www.jcancer.org/v11p6883.htm

File import instruction

Abstract

Objective: Anaplastic thyroid cancer/ATC is a highly aggressive malignancy with extremely poor prognosis. Resveratrol/Res promotes re-differentiation of cancer cells and exerts inhibitory effects on ATC cells. Sodium/iodide symporter/NIS and phosphate and tension homology deleted on chromsome ten/PTEN levels are positively correlated with the grade of thyroid cancer differentiation, while the impact of Res on them remain unknown.

Materials and Methods: The patterns of NIS and PTEN expression and intracellular distribution in THJ-16T and THJ-21T ATC and Nthy-ori 3-1 normal thyroid cells and their relevance with Res-caused ATC suppression were investigated via multiple experimental methods. E-cadherin was cited as a re-differentiation biomarker of ATC cells.

Results: MTT and EdU cell proliferation assays showed distinct growth suppression in ATC cells after Res treatment. TUNEL staining revealed extensive apoptosis of Res-treated THJ-16T and THJ-21T rather than Nthy-ori 3-1 cells. Western blotting, immunocytochemical/ICC and double-labeled immunofluorescent/IF staining showed increased PTEN levels accompanied with distinct NIS and PTEN nuclear co-translocation in Res-treated THJ-16T and THJ-21T cells. E-cadherin but not NIS appeared on the outer membrane.

Conclusion: PTEN upregulation and the concurrent NIS and PTEN nuclear translocation in Res-suppressed ATC cells may indicate the better therapeutic outcome and would be a group of beneficial prognostic factors of ATCs.

Keywords: PTEN, NIS, intracellular distribution, resveratrol, anaplastic thyroid cancer