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

被引:11
作者
Xu, Yipeng [1 ,2 ,3 ]
Pachnikova, Gabriela [4 ,5 ,6 ,7 ]
Wang, He
Wu, Yaoyao [8 ]
Przybilla, Dorothea [4 ,5 ,6 ,7 ]
Schaefer, Reinhold [4 ,5 ,6 ,7 ]
Chen, Zihao [9 ]
Zhu, Shaoxing [1 ,2 ,3 ]
Keilholz, Ulrich [4 ,5 ,6 ,7 ,10 ]
机构
[1] Univ Chinese Acad Sci, Canc Hosp, Dept Urol, Zhejiang Canc Hosp, Hangzhou, Peoples R China
[2] Key Lab Zhejiang Prov Aptamers & Theranost, Hangzhou, Peoples R China
[3] Chinese Acad Sci, Inst Basic Med & Canc, Hangzhou, Peoples R China
[4] Charite, Ctr Comprehens Canc, Berlin, Germany
[5] Free Univ Berlin, Berlin, Germany
[6] Humboldt Univ, Berlin, Germany
[7] Berlin Inst Hlth, Berlin, Germany
[8] Zhejiang Chinese Med Univ, Clin 2, Med Coll, Hangzhou, Zhejiang, Peoples R China
[9] Southern Med Univ, Dept Urol, Guangzhou, Peoples R China
[10] German Canc Consortium DKTK, Heidelberg, Germany
关键词
IC50; docetaxel; spheroids; drug testing; preclinical models; prostate cancer; 2D clinical models; 3D clinical models; cell culture; PATIENT-DERIVED XENOGRAFTS; MODELS; CULTURES; GROWTH;
D O I
10.17305/bjbms.2022.7279
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:580 / 592
页数:13
相关论文
共 53 条
[1]  
[Anonymous], BMC COMPLEM ALTERN M, DOI [DOI https://doi.org/10.1186/1472-6882-13-273, DOI 10.1615/INTERJFLUIDMECHRES.V42.I3.20]
[2]   TRIAL WATCH Phase III and submission failures: 2007-2010 [J].
Arrowsmith, John .
NATURE REVIEWS DRUG DISCOVERY, 2011, 10 (02) :1-1
[3]   High Throughput, Polymeric Aqueous Two-Phase Printing of Tumor Spheroids [J].
Atefi, Ehsan ;
Lemmo, Stephanie ;
Fyffe, Darcy ;
Luker, Gary D. ;
Tavana, Hossein .
ADVANCED FUNCTIONAL MATERIALS, 2014, 24 (41) :6509-6515
[4]  
Ballangrud ÅM, 1999, CLIN CANCER RES, V5, p3171S
[5]  
BAUMERT TF, 2019, VIRUSES BASEL, V11, DOI DOI https://doi.org/10.3390/v11050441
[6]  
Berrouet C, 2020, B MATH BIOL, V82, DOI 10.1007/s11538-020-00746-7
[7]  
Cho SY, 2020, LAB ANIM RES, V36
[8]  
Cohen-Kaplan Victoria, 2016, ONCOTARGET, V7, P83833, DOI [10.18632/oncotarget.13805, DOI 10.18632/ONCOTARGET.7564]
[9]   Sarcoma Spheroids and OrganoidsPromising Tools in the Era of Personalized Medicine [J].
Colella, Gianluca ;
Fazioli, Flavio ;
Gallo, Michele ;
De Chiara, Annarosaria ;
Apice, Gaetano ;
Ruosi, Carlo ;
Cimmino, Amelia ;
de Nigris, Filomena .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2018, 19 (02)
[10]   Modeling Physiological Events in 2D vs. 3D Cell Culture [J].
Duval, Kayla ;
Grover, Hannah ;
Han, Li-Hsin ;
Mou, Yongchao ;
Pegoraro, Adrian F. ;
Fredberg, Jeffery ;
Chen, Zi .
PHYSIOLOGY, 2017, 32 (04) :266-277