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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....

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Autores principales: Dubois, Clémence, Martin, Fanny, Hassel, Chervin, Magnier, Florian, Daumar, Pierre, Aubel, Corinne, Guerder, Sylvie, Mounetou, Emmanuelle, Penault-Lorca, Frédérique, Bamdad, Mahchid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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