Comparison of Drug Inhibitory Effects ($$\hbox {IC}_{50}$$) in Monolayer and Spheroid Cultures
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Abstract
Traditionally, the monolayer (two-dimensional) cell cultures are used for initial evaluation of the effectiveness of anticancer drugs. In particular, these experiments provide the IC50 curves that determine drug concentration that can inhibit growth of a tumor colony by half when compared to the cells grown with no exposure to the drug. Low IC50 value means that the drug is effective at low concentrations, and thus will show lower systemic toxicity when administered to the patient. However, in these experiments cells are grown in a monolayer, all well exposed to the drug, while in vivo tumors expand as three-dimensional multicellular masses, where inner cells have a limited access to the drug. Therefore, we performed computational studies to compare the IC50 curves for cells grown as a two-dimensional monolayer and a cross section through a three-dimensional spheroid. Our results identified conditions (drug diffusivity, drug action mechanisms and cell proliferation capabilities) under which these IC50 curves differ significantly. This will help experimentalists to better determine drug dosage for future in vivo experiments and clinical trials.
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Monolayer cell cultures may provide misleading results because IC50 values were almost identical for several cases in which spheroid cultures resulted in significantly distinct IC50 average values.
“Tuncer et al. explored drug inhibitory effects (IC50) in monolayer (2D) and spheroid (3D) cultures, indicating that monolayer cell cultures may provide misleading results, since the produced IC50 values were almost identical for several cases in which spheroid cultures resulted in significantly distinct IC50 average values25.”
From Tumor-on-a-chip: from bioinspired design to biomedical application (2021) · cites this paper as [25]
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Research works printed but not linked: 1
- Ascher UM, Ruuth SJ, Wetton BTR (1995) Implicit-explicit methods for time-dependent PDEs, SIAM. J Numer Anal 32(3): 797– 823
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Tumor-on-a-chip: from bioinspired design to biomedical application
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- Authors
- Berrouet, C., Dorilas, N., Rejniak, K. A., & Tuncer, N.
- Affiliations
- Florida Atlantic University (US)
- University of South Florida (US)
- Corresponding author
- Dorilas, Naika
- Rejniak, Katarzyna A.
- Tuncer, Necibe
- Venue
- Bulletin of Mathematical Biology
- Published
- 2020-06
- Volume
- 82
- Issue
- 6
- Pages
- 68-68
- ISSN
- 0092-8240 (ISSN-L)
- 1522-9602
- PMC
- PMC9773863
- OpenAlex
- W3029133261
- Cited by
- 133
- References
- 45
- Citations by year
- 2026: 19 · 2025: 40 · 2024: 34 · 2023: 22 · 2022: 11 · 2021: 6 · 2020: 1
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Bulletin of Mathematical Biology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (U01-CA202229-01)
- National Cancer Institute (P30-CA076292)
- Topics
- Physical Sciences › Mathematics › Modeling and Simulation › Mathematical Biology Tumor Growth
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mathematical and Theoretical Epidemiology and Ecology Models
- Keywords
- IC50, anticancer agents, tumor spheroids, monolayer culture, drug diffusion, 3D tumor models, drug efficacy, cell proliferation
- MeSH terms
- Antineoplastic Agents, Cell Survival, Computer Simulation, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Humans, Mitosis, Models, Biological, Neoplasms, Tumor Cells, Cultured, Spheroids, Cellular, Computational Biology, Cell Proliferation, Mathematical Concepts
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