PDF(Pubmed)
Abstract：
OBJECTIVE: 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.
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.
CONCLUSIONS: 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.
CONCLUSIONS: 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.
摘要：
目标：黑色素瘤，一种皮肤癌的变种，在所有皮肤癌中死亡率最高。尽管靶向治疗取得了进展，免疫疗法，和组织培养技术，缺乏有效的早期治疗模式仍然是一个挑战.这项研究调查了dabrafenib对具有不同分子谱的2D和3D细胞培养模型的影响。
方法：我们开发了一种高通量的工作流程，能够对球体进行药物筛选。我们的方法涉及培养源自正常黑素细胞和转移性黑色素瘤细胞的2D和3D培养物，用dabrafenib治疗并进行生存能力，聚合，迁移,细胞周期,和细胞凋亡测定。
结果：Dabrafenib施加了多方面的影响，特别是在浓度为10和25μM的迁移时。它诱导细胞活力下降，阻碍了细胞对基质的粘附，抑制细胞聚集和球状体形成，细胞周期停滞在G1期，诱导细胞凋亡。
结论：这些结果证实了dabrafenib在治疗具有BRAFV600E突变的黑色素瘤方面的治疗潜力，并且3D模型是研究新分子用于治疗目的的潜力的有效模型。此外，我们的研究强调了3D模型在模拟体内生理微环境中的相关性，提供对正常细胞和肿瘤细胞之间不同治疗反应的见解。
方法：我们开发了一种高通量的工作流程，能够对球体进行药物筛选。我们的方法涉及培养源自正常黑素细胞和转移性黑色素瘤细胞的2D和3D培养物，用dabrafenib治疗并进行生存能力，聚合，迁移,细胞周期,和细胞凋亡测定。
结果：Dabrafenib施加了多方面的影响，特别是在浓度为10和25μM的迁移时。它诱导细胞活力下降，阻碍了细胞对基质的粘附，抑制细胞聚集和球状体形成，细胞周期停滞在G1期，诱导细胞凋亡。
结论：这些结果证实了dabrafenib在治疗具有BRAFV600E突变的黑色素瘤方面的治疗潜力，并且3D模型是研究新分子用于治疗目的的潜力的有效模型。此外，我们的研究强调了3D模型在模拟体内生理微环境中的相关性，提供对正常细胞和肿瘤细胞之间不同治疗反应的见解。
