title: A Novel Multiparametric Drug-Scoring Method for High-Throughput Screening of 3D Multicellular Tumor Spheroids Using the Celigo Image Cytometer.
abstract: Three-dimensional (3D) tumor models have been increasingly used to investigate and characterize cancer drug compounds. The ability to perform high-throughput screening of 3D multicellular tumor spheroids (MCTS) can highly improve the efficiency and cost-effectiveness of discovering potential cancer drug candidates. Previously, the Celigo Image Cytometer has demonstrated a novel method for high-throughput screening of 3D multicellular tumor spheroids. In this work, we employed the Celigo Image Cytometer to examine the effects of 14 cancer drug compounds on 3D MCTS of the glioblastoma cell line U87MG in 384-well plates. Using parameters such as MCTS diameter and invasion area, growth and invasion were monitored for 9 and 3 d, respectively. Furthermore, fluorescent staining with calcein AM, propidium iodide, Hoechst 33342, and caspase 3/7 was performed at day 9 posttreatment to measure viability and apoptosis. Using the kinetic and endpoint data generated, we created a novel multiparametric drug-scoring system for 3D MCTS that can be used to identify and classify potential drug candidates earlier in the drug discovery process. Furthermore, the combination of quantitative and qualitative image data can be used to delineate differences between drugs that induce cytotoxic and cytostatic effects. The 3D MCTS-based multiparametric scoring method described here can provide an alternative screening method to better qualify tested drug compounds.
authors.affiliation: 1 Department of Technology R&D, Nexcelom Bioscience LLC, Lawrence, MA, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Cribbes
authors.affiliation: 1 Department of Technology R&D, Nexcelom Bioscience LLC, Lawrence, MA, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kessel
authors.affiliation: 1 Department of Technology R&D, Nexcelom Bioscience LLC, Lawrence, MA, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: McMenemy
authors.affiliation: 1 Department of Technology R&D, Nexcelom Bioscience LLC, Lawrence, MA, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Qiu
authors.affiliation: 1 Department of Technology R&D, Nexcelom Bioscience LLC, Lawrence, MA, USA.
authors.forename: Leo Li-Ying
authors.initials: LL
authors.lastname: Chan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D055808:Drug Discovery / Q000379:methods; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D019044:Image Cytometry / Q000379:methods; D018874:Spheroids, Cellular / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D020169:Caspases
keywords: 3D multicellular tumor spheroid (MCTS); Celigo; growth inhibition; high-throughput; image cytometry; invasion assay; spheroid apoptosis; spheroid viability