Comparative Analysis of the Effect of the BRAF Inhibitor Dabrafenib in 2D and 3D Cell Culture Models of Human Metastatic Melanoma Cells

BRAF 抑制剂达拉非尼在人类转移性黑色素瘤细胞 2D 和 3D 细胞培养模型中的作用比较分析

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作者:David Tovar-Parra, Marion Zammit-Mangion

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 and

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.

Methods

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.

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