Comparative Analysis of the Effect of the BRAF Inhibitor Dabrafenib in 2D and 3D Cell Culture Models of Human Metastatic Melanoma Cells.
In Vivo
; 38(4): 1579-1593, 2024.
Article
en En
| MEDLINE
| ID: mdl-38936891
ABSTRACT
BACKGROUND/AIM:
Melanoma, a variant of skin cancer, presents the highest mortality rates among all skin cancers. Despite advancements in targeted therapies, immunotherapies, and tissue culture techniques, the absence of an effective early treatment model remains a challenge. This study investigated the impact of dabrafenib on both 2D and 3D cell culture models with distinct molecular profiles. MATERIALS ANDMETHODS:
We developed a high-throughput workflow enabling drug screening on spheroids. Our approach involved cultivating 2D and 3D cultures derived from normal melanocytes and metastatic melanoma cells, treating them with dabrafenib and conducting viability, aggregation, migration, cell cycle, and apoptosis assays.RESULTS:
Dabrafenib exerted multifaceted influences, particularly on migration at concentrations of 10 and 25 µM. It induced a decrease in cell viability, impeded cellular adhesion to the matrix, inhibited cellular aggregation and spheroid formation, arrested the cell cycle in the G1 phase, and induced apoptosis.CONCLUSION:
These results confirm the therapeutic potential of dabrafenib in treating melanoma with the BRAF V600E mutation and that 3D models are validated models to study the potential of new molecules for therapeutic purposes. Furthermore, our study underscores the relevance of 3D models in simulating physiological in vivo microenvironments, providing insights into varied treatment responses between normal and tumor cells.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oximas
/
Movimiento Celular
/
Supervivencia Celular
/
Apoptosis
/
Esferoides Celulares
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Proteínas Proto-Oncogénicas B-raf
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Imidazoles
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Melanoma
Límite:
Humans
Idioma:
En
Revista:
In Vivo
Asunto de la revista:
NEOPLASIAS
Año:
2024
Tipo del documento:
Article