IC50: an unsuitable measure for large-sized prostate cancer spheroids in drug sensitivity evaluation

Yipeng Xu; Gabriela Pachnikova; He Wang; Yaoyao Wu; Dorothea  Przybilla; Reinhold Schäfer; Zihao Chen; Shaoxing  Zhu; Ulrich Keilholz

doi:10.17305/bjbms.2022.7279

Authors

Yipeng Xu 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 https://orcid.org/0000-0003-4775-4160
Gabriela Pachnikova Comprehensive Cancer Center, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
He Wang The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
Yaoyao Wu The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
Dorothea Przybilla Comprehensive Cancer Center, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
Reinhold Schäfer Comprehensive Cancer Center, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
Zihao Chen Department of Urology, Southern Medical University, Guangzhou, China
Shaoxing Zhu 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
Ulrich Keilholz Comprehensive Cancer Center, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany

DOI:

https://doi.org/10.17305/bjbms.2022.7279

Keywords:

IC50, docetaxel, spheroids, drug testing, preclinical models, prostate cancer, 2D clinical models, 3D clinical models, cell culture

Abstract

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.