Department of Urology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China; The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Hangzhou, China; Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.
Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Bosn J Basic Med Sci. 2022 Jul 29;22(4):580-592. doi: 10.17305/bjbms.2022.7279.
Preclinical models of tumors have the potential to become valuable tools for commercial drug research and development, and 3D culture systems are gaining traction in this area, particularly in prostate cancer (PCa) research. However, nearly all 3D drug design and screening assessments are based on 2D experiments, suggesting 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 in the drug docetaxel, as well as the sensitivity of different morphologies of 2D/3D LNCaP to docetaxel treatment. In contrast to 2D LNCaP cells, the evaluation of LNCaP spheroids' susceptibility to treatment was more complicated; the fitness of IC50 curves of 2D and 3D tumor cell preclinical models differs significantly. IC50 curves were unsuitable for large-sized LNCaP spheroids. More evaluation indexes (such as max inhibition) and experiments (such as spheroids formation) should be explored and performed to evaluate the susceptibility systematically.
肿瘤的临床前模型有可能成为商业药物研发的有价值的工具,而 3D 培养系统在这一领域越来越受到关注,特别是在前列腺癌 (PCa) 研究中。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 药物测试存在局限性。为了模拟人类细胞对药物的自然反应,我们检测了 2D/3D LNCaP 细胞在药物多西紫杉醇中的半最大抑制浓度 (IC50) 变化,以及不同形态的 2D/3D LNCaP 对多西紫杉醇治疗的敏感性。与 2D LNCaP 细胞相比,评估 LNCaP 球体对治疗的敏感性更加复杂;2D 和 3D 肿瘤细胞临床前模型的 IC50 曲线拟合度差异显著。IC50 曲线不适合大尺寸的 LNCaP 球体。应该探索和进行更多的评估指标(如最大抑制)和实验(如球体形成),以系统地评估敏感性。