High-throughput screening reveals higher synergistic effect of MEK inhibitor combinations in colon cancer spheroids.
Sci Rep
; 10(1): 11574, 2020 07 14.
Article
en En
| MEDLINE
| ID: mdl-32665693
ABSTRACT
Drug combinations have been proposed to combat drug resistance, but putative treatments are challenged by low bench-to-bed translational efficiency. To explore the effect of cell culture format and readout methods on identification of synergistic drug combinations in vitro, we studied response to 21 clinically relevant drug combinations in standard planar (2D) layouts and physiologically more relevant spheroid (3D) cultures of HCT-116, HT-29 and SW-620 cells. By assessing changes in viability, confluency and spheroid size, we were able to identify readout- and culture format-independent synergies, as well as synergies specific to either culture format or readout method. In particular, we found that spheroids, compared to 2D cultures, were generally both more sensitive and showed greater synergistic response to combinations involving a MEK inhibitor. These results further shed light on the importance of including more complex culture models in order to increase the efficiency of drug discovery pipelines.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias del Colon
/
Quinasas de Proteína Quinasa Activadas por Mitógenos
/
Inhibidores de Proteínas Quinasas
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Detección Precoz del Cáncer
Tipo de estudio:
Diagnostic_studies
/
Screening_studies
Límite:
Humans
Idioma:
En
Año:
2020
Tipo del documento:
Article