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Open AccessArticle

Low-Dose and Long-Term Olaparib Treatment Sensitizes MDA-MB-231 and SUM1315 Triple-Negative Breast Cancers Spheroids to Fractioned Radiotherapy

1
Université Clermont Auvergne, Centre Jean Perrin, INSERM, U1240, Imagerie Moléculaire et Stratégies Théranostiques, F-63000 Clermont Ferrand, France
2
Université Clermont Auvergne, Institut Universitaire de Technologie, INSERM, U1240, Imagerie Moléculaire et Stratégies Théranostiques, F-63000 Clermont Ferrand, France
3
Département de Radiothérapie, Centre Jean Perrin, F-63000 Clermont Ferrand, France
4
Centre Hospitalier Universitaire Purpan, Centre de Physiopathologie de Toulouse Purpan, INSERM, UMR 1043/CNRS UMR 5282, Antigen Presenting Cells and CD4 T cell responses, F-31024 Toulouse, France
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Service de Physique Médicale, Centre Jean Perrin, F-63000 Clermont Ferrand, France
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Université Clermont Auvergne, Faculté de Médecine, INSERM, U1240, Imagerie Moléculaire et Stratégies Théranostiques, F-63000 Clermont Ferrand, France
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Clin. Med. 2020, 9(1), 64; https://doi.org/10.3390/jcm9010064
Received: 29 November 2019 / Revised: 20 December 2019 / Accepted: 23 December 2019 / Published: 26 December 2019
(This article belongs to the Section Oncology)
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. View Full-Text
Keywords: Triple-Negative Breast Cancer; SUM1315; MDA-MB-231; PARPi Olaparib; fractioned radiotherapy; co-treatment; the three-dimensional cell culture; spheroid; transcriptomic analysis Triple-Negative Breast Cancer; SUM1315; MDA-MB-231; PARPi Olaparib; fractioned radiotherapy; co-treatment; the three-dimensional cell culture; spheroid; transcriptomic analysis
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Dubois, C.; Martin, F.; Hassel, C.; Magnier, F.; Daumar, P.; Aubel, C.; Guerder, S.; Mounetou, E.; Penault-Lorca, F.; Bamdad, M. Low-Dose and Long-Term Olaparib Treatment Sensitizes MDA-MB-231 and SUM1315 Triple-Negative Breast Cancers Spheroids to Fractioned Radiotherapy. J. Clin. Med. 2020, 9, 64.

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