Comparison of Drug Inhibitory Effects ([Formula: see text]) in Monolayer and Spheroid Cultures

Bull Math Biol. 2020 Jun 3;82(6):68. doi: 10.1007/s11538-020-00746-7.

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 [Formula: see text] 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 [Formula: see text] 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 [Formula: see text] 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 [Formula: see text] curves differ significantly. This will help experimentalists to better determine drug dosage for future in vivo experiments and clinical trials.

Keywords: Drugs efficacy; Monolayer versus spheroid cell cultures; values.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / toxicity
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Computational Biology
  • Computer Simulation
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor / methods
  • Drug Screening Assays, Antitumor / statistics & numerical data
  • Humans
  • Mathematical Concepts
  • Mitosis / drug effects
  • Models, Biological
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Spheroids, Cellular / drug effects*
  • Spheroids, Cellular / metabolism
  • Spheroids, Cellular / pathology
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents