Time- and Dose-Dependent Toxicity Studies in 3D Cultures Using a Luminescent Lactate Dehydrogenase Assay

Methods Mol Biol. 2021:2255:77-86. doi: 10.1007/978-1-0716-1162-3_8.

Abstract

Three-dimensional (3D) in vitro systems closely resemble tissue microenvironments and provide predictive models for studying cytotoxic drug responses. The ability to capture the kinetic profiles of such responses in a dynamic and noninvasive way can further advance the utility of 3D cell cultures. Here, we describe the use of a luminescent lactate dehydrogenase (LDH) toxicity assay for monitoring time- and dose-dependent effects of drug treatment in 3D cancer spheroids. HCT116 spheroids formed in 96-well ultralow attachment plates were treated with increasing drug concentrations. Medium samples were collected at different timepoints, frozen, stored, and analyzed at the end of experiments using the luminescent LDH-Glo™ Assay. High assay sensitivity and low volume sampling enabled drug-induced toxicity profiling in a time- and dose-dependent manner.

Keywords: 3D spheroids; 96-well ultralow attachment plates; LDH; LDH-Glo; Time-dependent cytotoxicity.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Digitonin / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor / methods*
  • Humans
  • Indicators and Reagents / pharmacology
  • L-Lactate Dehydrogenase / metabolism*
  • Luminescent Measurements / methods*
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Spheroids, Cellular / drug effects
  • Spheroids, Cellular / metabolism
  • Spheroids, Cellular / pathology*
  • Time Factors
  • Toxicity Tests / methods*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Indicators and Reagents
  • L-Lactate Dehydrogenase
  • Digitonin