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Low-Dose and Long-Term Olaparib Treatment Sensitizes MDA-MB-231 and SUM1315 Triple-Negative Breast Cancers Spheroids to Fractioned Radiotherapy
The Triple-Negative Breast Cancer subtype (TNBC) is particularly aggressive and heterogeneous. Thus, Poly-ADP-Ribose Polymerase inhibitors were developed to improve the prognosis of patients and treatment protocols are still being evaluated. In this context, we modelized the efficacy of Olaparib (i....
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019977/ https://www.ncbi.nlm.nih.gov/pubmed/31888054 http://dx.doi.org/10.3390/jcm9010064 |
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author | Dubois, Clémence Martin, Fanny Hassel, Chervin Magnier, Florian Daumar, Pierre Aubel, Corinne Guerder, Sylvie Mounetou, Emmanuelle Penault-Lorca, Frédérique Bamdad, Mahchid |
author_facet | Dubois, Clémence Martin, Fanny Hassel, Chervin Magnier, Florian Daumar, Pierre Aubel, Corinne Guerder, Sylvie Mounetou, Emmanuelle Penault-Lorca, Frédérique Bamdad, Mahchid |
author_sort | Dubois, Clémence |
collection | PubMed |
description | The Triple-Negative Breast Cancer subtype (TNBC) is particularly aggressive and heterogeneous. Thus, Poly-ADP-Ribose Polymerase inhibitors were developed to improve the prognosis of patients and treatment protocols are still being evaluated. In this context, we modelized the efficacy of Olaparib (i.e., 5 and 50 µM), combined with fractioned irradiation (i.e., 5 × 2 Gy) on two aggressive TNBC cell lines MDA-MB-231 (BRCAness) and SUM1315 (BRCA1-mutated). In 2D cell culture and for both models, the clonogenicity drop was 95-fold higher after 5 µM Olaparib and 10 Gy irradiation than Olaparib treatment alone and was only 2-fold higher after 50 µM and 10 Gy. Similar responses were obtained on TNBC tumor-like spheroid models after 10 days of co-treatment. Indeed, the ratio of metabolic activity decrease was of 1.2 for SUM1315 and 3.3 for MDA-MB-231 after 5 µM and 10 Gy and of only 0.9 (both models) after 50 µM and 10 Gy. MDA-MB-231, exhibiting a strong proliferation profile and an overexpression of AURKA, was more sensitive to the co-treatment than SUM1315 cell line, with a stem-cell like phenotype. These results suggest that, with the studied models, the potentiation of Olaparib treatment could be reached with low-dose and long-term exposure combined with fractioned irradiation. |
format | Online Article Text |
id | pubmed-7019977 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70199772020-03-09 Low-Dose and Long-Term Olaparib Treatment Sensitizes MDA-MB-231 and SUM1315 Triple-Negative Breast Cancers Spheroids to Fractioned Radiotherapy Dubois, Clémence Martin, Fanny Hassel, Chervin Magnier, Florian Daumar, Pierre Aubel, Corinne Guerder, Sylvie Mounetou, Emmanuelle Penault-Lorca, Frédérique Bamdad, Mahchid J Clin Med Article The Triple-Negative Breast Cancer subtype (TNBC) is particularly aggressive and heterogeneous. Thus, Poly-ADP-Ribose Polymerase inhibitors were developed to improve the prognosis of patients and treatment protocols are still being evaluated. In this context, we modelized the efficacy of Olaparib (i.e., 5 and 50 µM), combined with fractioned irradiation (i.e., 5 × 2 Gy) on two aggressive TNBC cell lines MDA-MB-231 (BRCAness) and SUM1315 (BRCA1-mutated). In 2D cell culture and for both models, the clonogenicity drop was 95-fold higher after 5 µM Olaparib and 10 Gy irradiation than Olaparib treatment alone and was only 2-fold higher after 50 µM and 10 Gy. Similar responses were obtained on TNBC tumor-like spheroid models after 10 days of co-treatment. Indeed, the ratio of metabolic activity decrease was of 1.2 for SUM1315 and 3.3 for MDA-MB-231 after 5 µM and 10 Gy and of only 0.9 (both models) after 50 µM and 10 Gy. MDA-MB-231, exhibiting a strong proliferation profile and an overexpression of AURKA, was more sensitive to the co-treatment than SUM1315 cell line, with a stem-cell like phenotype. These results suggest that, with the studied models, the potentiation of Olaparib treatment could be reached with low-dose and long-term exposure combined with fractioned irradiation. MDPI 2019-12-26 /pmc/articles/PMC7019977/ /pubmed/31888054 http://dx.doi.org/10.3390/jcm9010064 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Dubois, Clémence Martin, Fanny Hassel, Chervin Magnier, Florian Daumar, Pierre Aubel, Corinne Guerder, Sylvie Mounetou, Emmanuelle Penault-Lorca, Frédérique Bamdad, Mahchid Low-Dose and Long-Term Olaparib Treatment Sensitizes MDA-MB-231 and SUM1315 Triple-Negative Breast Cancers Spheroids to Fractioned Radiotherapy |
title | Low-Dose and Long-Term Olaparib Treatment Sensitizes MDA-MB-231 and SUM1315 Triple-Negative Breast Cancers Spheroids to Fractioned Radiotherapy |
title_full | Low-Dose and Long-Term Olaparib Treatment Sensitizes MDA-MB-231 and SUM1315 Triple-Negative Breast Cancers Spheroids to Fractioned Radiotherapy |
title_fullStr | Low-Dose and Long-Term Olaparib Treatment Sensitizes MDA-MB-231 and SUM1315 Triple-Negative Breast Cancers Spheroids to Fractioned Radiotherapy |
title_full_unstemmed | Low-Dose and Long-Term Olaparib Treatment Sensitizes MDA-MB-231 and SUM1315 Triple-Negative Breast Cancers Spheroids to Fractioned Radiotherapy |
title_short | Low-Dose and Long-Term Olaparib Treatment Sensitizes MDA-MB-231 and SUM1315 Triple-Negative Breast Cancers Spheroids to Fractioned Radiotherapy |
title_sort | low-dose and long-term olaparib treatment sensitizes mda-mb-231 and sum1315 triple-negative breast cancers spheroids to fractioned radiotherapy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019977/ https://www.ncbi.nlm.nih.gov/pubmed/31888054 http://dx.doi.org/10.3390/jcm9010064 |
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