Open Access

Iodine‑131 metabolic radiotherapy leads to cell death and genomic alterations through NIS overexpression on cholangiocarcinoma

  • Authors:
    • Ana Filipa Brito
    • Ana Margarida Abrantes
    • Ricardo Teixo
    • Ana Salomé Pires
    • Ana Cláudia Ribeiro
    • Rafael Fernandes Ferreira
    • Alexandra Mascarenhas
    • Tiago Puga
    • Mafalda Laranjo
    • Francisco Caramelo
    • Ilka Boin
    • Douglas M. Jefferson
    • Cristina Gonçalves
    • Ricardo Martins
    • Inês Tavares
    • Ilda Patrícia Ribeiro
    • Ana Bela Sarmento-Ribeiro
    • Isabel Marques Carreira
    • Doroteia Souza
    • José Guilherme Tralhão
    • Maria Filomena Botelho
  • View Affiliations

  • Published online on: January 10, 2020     https://doi.org/10.3892/ijo.2020.4957
  • Pages: 709-727
  • Copyright: © Brito et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Cholangiocarcinoma (CC) is an aggressive liver tumor with limited therapeutic options. Natrium‑iodide symporter (NIS) mediates the uptake of iodine by the thyroid, representing a key component in metabolic radiotherapy using iodine‑131 (131I) for the treatment of thyroid cancer. NIS expression is increased in CC, providing the opportunity for a novel therapeutic approach for this type of tumor. Thus, in this study, we aimed to evaluate therapeutic efficacy of 131I in two human CC cell lines. Uptake experiments analyzed the 131I uptake profiles of the tumor cell lines under study. The cells were irradiated with various doses of 131I to evaluate and characterize the effects of metabolic radiotherapy. NIS protein expression was assessed by immunofluorescence methods. Cell survival was evaluated by clonogenic assay and flow cytometry was used to assess cell viability, and the type of death and alterations in the cell cycle. The genomic and epigenetic characterization of both CC cells was performed before and after irradiation. NIS gene expression was evaluated in the CC cells by RT‑qPCR. The results revealed that CC cells had a higher expression of NIS. 131I induced a decrease in cell survival in a dose‑dependent manner. With the increasing irradiation dose, a decrease in cell viability was observed, with a consequent increase in cell death by initial apoptosis. Karyotype and array comparative genomic hybridization (aCGH) analyses revealed that both CC cell lines were near‑triploid with several numerical and structural chromosomal rearrangements. NIS gene expression was increased in the TFK‑1 and HuCCT1 cells in a time‑dependent manner. On the whole, the findings of this study demonstrate that the presence of NIS in cholangiocarcinoma cell lines is crucial for the decreased cell viability and survival observed following the exposure of cholangiocarcinoma cells to 131I.
View Figures
View References

Related Articles

Journal Cover

March 2020
Volume 56 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
APA
Brito, A.F., Abrantes, A.M., Teixo, R., Pires, A.S., Ribeiro, A.C., Ferreira, R.F. ... Botelho, M.F. (2020). Iodine‑131 metabolic radiotherapy leads to cell death and genomic alterations through NIS overexpression on cholangiocarcinoma. International Journal of Oncology, 56, 709-727. https://doi.org/10.3892/ijo.2020.4957
MLA
Brito, A. F., Abrantes, A. M., Teixo, R., Pires, A. S., Ribeiro, A. C., Ferreira, R. F., Mascarenhas, A., Puga, T., Laranjo, M., Caramelo, F., Boin, I., Jefferson, D. M., Gonçalves, C., Martins, R., Tavares, I., Ribeiro, I. P., Sarmento-Ribeiro, A. B., Carreira, I. M., Souza, D., Tralhão, J. ., Botelho, M. F."Iodine‑131 metabolic radiotherapy leads to cell death and genomic alterations through NIS overexpression on cholangiocarcinoma". International Journal of Oncology 56.3 (2020): 709-727.
Chicago
Brito, A. F., Abrantes, A. M., Teixo, R., Pires, A. S., Ribeiro, A. C., Ferreira, R. F., Mascarenhas, A., Puga, T., Laranjo, M., Caramelo, F., Boin, I., Jefferson, D. M., Gonçalves, C., Martins, R., Tavares, I., Ribeiro, I. P., Sarmento-Ribeiro, A. B., Carreira, I. M., Souza, D., Tralhão, J. ., Botelho, M. F."Iodine‑131 metabolic radiotherapy leads to cell death and genomic alterations through NIS overexpression on cholangiocarcinoma". International Journal of Oncology 56, no. 3 (2020): 709-727. https://doi.org/10.3892/ijo.2020.4957