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IC50: an unsuitable measure for large-sized prostate cancer spheroids in drug sensitivity evaluation.
Biomolecules and Biomedicine ( IF 3.4 ) Pub Date : 2022-06-09 , DOI: 10.17305/bjbms.2022.7279
Yipeng Xu 1 , Gabriela Pachnikova 2 , He Wang 3 , Yaoyao Wu 3 , Dorothea Przybilla 2 , Reinhold Schäfer 2 , Zihao Chen 4 , Shaoxing Zhu 1 , Ulrich Keilholz 5
Affiliation  

Preclinical models of tumors have the potential to become valuable tools for commercial drug research and development, and 3D culture systems are gaining attraction in this area, including prostate cancer (PCa) research. However, nearly all 3D drug design and screening assessments are based on 2D experiments, indicating the limitations of 3D drug testing. To simulate the natural response of human cells to the drug, we detected the half-maximal inhibitory concentration (IC50) changes of 2D/3D LNCaP cells to the drug docetaxel and the sensitivity of different morphologies of 2D/3D LNCaP to docetaxel treatment. In contrast to 2D LNCaP cells, the evaluation of the susceptibility of LNCaP spheroids to treatment was more complicated. The fitness of IC50 curves of 2D and 3D tumor cell preclinical models differed significantly. IC50curves were unsuitable for large LNCaP spheroids. More evaluation indexes (e.g., maximal inhibition) and experiments (e.g., spheroids formation) should be explored and performed to systematically evaluate the susceptibility.

中文翻译:

IC50:药物敏感性评估中大尺寸前列腺癌球体的不合适测量。

肿瘤的临床前模型有可能成为商业药物研发的宝贵工具,并且 3D 培养系统在这一领域越来越受欢迎,包括前列腺癌 (PCa) 研究。然而,几乎所有的 3D 药物设计和筛选评估都是基于 2D 实验,这表明 3D 药物测试的局限性。为了模拟人体细胞对药物的自然反应,我们检测了 2D/3D LNCaP 细胞对药物多西他赛的半数最大抑制浓度 (IC50) 变化以及不同形态的 2D/3D LNCaP 对多西他赛治疗的敏感性。与二维 LNCaP 细胞相比,LNCaP 球体对治疗的敏感性评估更为复杂。2D 和 3D 肿瘤细胞临床前模型的 IC50 曲线的拟合度存在显着差异。IC50 曲线不适用于大型 LNCaP 球体。应探索和进行更多的评价指标(例如,最大抑制)和实验(例如,球体形成)以系统地评估易感性。
更新日期:2022-06-09
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