دورية أكاديمية
High-Content Monitoring of Drug Effects in a 3D Spheroid Model
| العنوان: | High-Content Monitoring of Drug Effects in a 3D Spheroid Model |
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| المؤلفون: | Mittler, Frédérique, Obeïd, Patricia, Rulina, Anastasiia V., Haguet, Vincent, Gidrol, Xavier, Balakirev, Maxim Y. |
| المساهمون: | Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes 2016-2019 (UGA 2016-2019 )-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Inflammasome NLRP3 – NLRP3 Inflammasome, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-11-NANB-0002,FACSBIOMARKER,Identification et validation de biomarqueurs du cancer de la prostate par ARN interférence à haut débit couplée au FACS(2011) |
| المصدر: | ISSN: 2234-943X ; Frontiers in Oncology ; https://hal.science/hal-01911334Test ; Frontiers in Oncology, 2017, 7, pp.293. ⟨10.3389/fonc.2017.00293⟩. |
| بيانات النشر: | HAL CCSD Frontiers |
| سنة النشر: | 2017 |
| المجموعة: | HAL-CEA (Commissariat à l'énergie atomique et aux énergies alternatives) |
| مصطلحات موضوعية: | spheroids, ubiquitin, prostate cancer, Nedd8, 3D model, drug discovery, HCS screening, MLN4924, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology |
| الوصف: | International audience ; A recent decline in the discovery of novel medications challenges the widespread use of 2D monolayer cell assays in the drug discovery process. As a result, the need for more appropriate cellular models of human physiology and disease has renewed the interest in spheroid 3D culture as a pertinent model for drug screening. However, despite technological progress that has significantly simplified spheroid production and analysis, the seeming complexity of the 3D approach has delayed its adoption in many laboratories. The present report demonstrates that the use of a spheroid model may be straightforward and can provide information that is not directly available with a standard 2D approach. We describe a cost-efficient method that allows for the production of an array of uniform spheroids, their staining with vital dyes, real-time monitoring of drug effects, and an ATP-endpoint assay, all in the same 96-well U-bottom plate. To demonstrate the method performance, we analyzed the effect of the preclinical anticancer drug MLN4924 on spheroids formed by VCaP and LNCaP prostate cancer cells. The drug has different outcomes in these cell lines, varying from cell cycle arrest and protective dormancy to senescence and apoptosis. We demonstrate that by using high-content analysis of spheroid arrays, the effect of the drug can be described as a series of EC50 values that clearly dissect the cytostatic and cytotoxic drug actions. The method was further evaluated using four standard cancer chemotherapeutics with different mechanisms of action, and the effect of each drug is described as a unique multi-EC50 diagram. Once fully validated in a wider range of conditions, this method could be particularly valuable for phenotype-based drug discovery. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/29322028; hal-01911334; https://hal.science/hal-01911334Test; PUBMED: 29322028; PUBMEDCENTRAL: PMC5732143 |
| DOI: | 10.3389/fonc.2017.00293 |
| الإتاحة: | https://doi.org/10.3389/fonc.2017.00293Test https://hal.science/hal-01911334Test |
| رقم الانضمام: | edsbas.B47CAF51 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fonc.2017.00293 |
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