Iodine-131 metabolic radiotherapy leads to cell death and genomic alterations through NIS overexpression on cholangiocarcinoma
| Autor: | Ana Brito, Ana Abrantes, Ricardo Teixo, Ana Pires, Ana Ribeiro, Rafael Ferreira, Alexandra Fernandes, Tiago Puga, Mafalda Laranjo, Francisco Caramelo, Ilka Boin, Douglas Jefferson, Ana Gon�alves, Ricardo Martins, Joana Rodrigues, Ilda Ribeiro, Joana Barbosa De Melo, Ana Sarmento-Ribeiro, Isabel Carreira, Doroteia Souza, Jos� Guilherme Tralh�o, Maria Botelho |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
DNA Copy Number Variations Cell Survival Cell Biology Flow cytometry Cholangiocarcinoma Iodine Radioisotopes 03 medical and health sciences 0302 clinical medicine Cell Line Tumor medicine Humans Viability assay Clonogenic assay Oncogene medicine.diagnostic_test Cell Death Symporters Cell Cycle iodine-131 Dose-Response Relationship Radiation Articles Cell cycle metabolic radiotherapy DNA Methylation 3. Good health Gene Expression Regulation Neoplastic medicine.anatomical_structure Oncology Bile Duct Neoplasms Apoptosis Cell culture 030220 oncology & carcinogenesis natrium-iodide symporter Genomic Structural Variation Cancer research gene expression 030211 gastroenterology & hepatology |
| Zdroj: | International Journal of Oncology |
| ISSN: | 1791-2423 1019-6439 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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