Low-Dose and Long-Term Olaparib Treatment Sensitizes MDA-MB-231 and SUM1315 Triple-Negative Breast Cancers Spheroids to Fractioned Radiotherapy
| Autor: | Corinne Aubel, Frédérique Penault-Lorca, F. Magnier, Clémence Dubois, Emmanuelle Mounetou, Mahchid Bamdad, Fanny Martin, Pierre Daumar, Chervin Hassel, Sylvie Guerder |
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| Přispěvatelé: | Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Centre de Physiopathologie de Toulouse-Purpan (INSERM U563 - CNRS UMR1037), Centre National de la Recherche Scientifique (CNRS)-Centre de lutte contre le cancer (CLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Institut Claudius Regaud, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_treatment
lcsh:Medicine [SDV.CAN]Life Sciences [q-bio]/Cancer Context (language use) [SDV.BC]Life Sciences [q-bio]/Cellular Biology Article Olaparib 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine the three-dimensional cell culture sum1315 Medicine Triple negative parpi olaparib Triple-negative breast cancer transcriptomic analysis 030304 developmental biology Mda mb 231 0303 health sciences business.industry mda-mb-231 lcsh:R Spheroid General Medicine fractioned radiotherapy 3. Good health Radiation therapy co-treatment chemistry Cell culture spheroid 030220 oncology & carcinogenesis Cancer research triple-negative breast cancer business |
| Zdroj: | Journal of Clinical Medicine, Vol 9, Iss 1, p 64 (2019) Journal of Clinical Medicine Journal of Clinical Medicine, MDPI, 2019, 9 (1), pp.64. ⟨10.3390/jcm9010064⟩ Journal of Clinical Medicine, 2019, 9 (1), pp.64. ⟨10.3390/jcm9010064⟩ Volume 9 Issue 1 |
| ISSN: | 2077-0383 |
| DOI: | 10.3390/jcm9010064⟩ |
| Popis: | 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 µ M), 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 µ M Olaparib and 10 Gy irradiation than Olaparib treatment alone and was only 2-fold higher after 50 µ M 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 µ M and 10 Gy and of only 0.9 (both models) after 50 µ M 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. |
| Databáze: | OpenAIRE |
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