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Comparison of drug inhibitory effects (IC50) in monolayer and spheroid cultures

Catherine Berrouet, Naika Dorilas, View ORCID ProfileKatarzyna A. Rejniak, View ORCID ProfileNecibe Tuncer
doi: https://doi.org/10.1101/2020.05.05.079285
Catherine Berrouet
1Department of Mathematical Sciences, Charles E. Schmidt College of Science, Florida Atlantic University, Boca Raton FL
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Naika Dorilas
1Department of Mathematical Sciences, Charles E. Schmidt College of Science, Florida Atlantic University, Boca Raton FL
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Katarzyna A. Rejniak
2Integrated Mathematical Oncology Department, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL
3Department of Oncologic Sciences, Morsani College of Medicine, University of South Florida, Tampa, FL
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Necibe Tuncer
1Department of Mathematical Sciences, Charles E. Schmidt College of Science, Florida Atlantic University, Boca Raton FL
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Abstract

Traditionally, the monolayer (two-dimensional) cell cultures are used for initial evaluation of the ef-fectiveness 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.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 06, 2020.
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Comparison of drug inhibitory effects (IC50) in monolayer and spheroid cultures
Catherine Berrouet, Naika Dorilas, Katarzyna A. Rejniak, Necibe Tuncer
bioRxiv 2020.05.05.079285; doi: https://doi.org/10.1101/2020.05.05.079285
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Comparison of drug inhibitory effects (IC50) in monolayer and spheroid cultures
Catherine Berrouet, Naika Dorilas, Katarzyna A. Rejniak, Necibe Tuncer
bioRxiv 2020.05.05.079285; doi: https://doi.org/10.1101/2020.05.05.079285

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