title: Evaluation by quantitative image analysis of anticancer drug activity on multicellular spheroids grown in 3D matrices.
abstract: Pharmacological evaluation of anticancer drugs using 3Din vitromodels provides invaluable information for predictingin vivoactivity. Artificial matrices are currently available that scale up and increase the power of such 3D models. The aim of the present study was to propose an efficient and robust imaging and analysis pipeline to assess with quantitative parameters the efficacy of a particular cytotoxic drug. HCT116 colorectal adenocarcinoma tumor cell multispheres were grown in a 3D physiological hyaluronic acid matrix. 3D microscopy was performed with structured illumination, whereas image processing and feature extraction were performed with custom analysis tools. This procedure makes it possible to automatically detect spheres in a large volume of matrix in 96-well plates. It was used to evaluate drug efficacy in HCT116 spheres treated with different concentrations of topotecan, a DNA topoisomerase inhibitor. Following automatic detection and quantification, changes in cluster size distribution with a topotecan concentration-dependent increase of small clusters according to drug cytotoxicity were observed. Quantitative image analysis is thus an effective means to evaluate and quantify the cytotoxic and cytostatic activities of anticancer drugs on 3D multicellular models grown in a physiological matrix.
authors.affiliation: Institut des Technologies Avancées en sciences du Vivant, Centre National de la Recherche Scientifique, Université Paul Sabatier, Université de Toulouse, 31106 Toulouse, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Gomes
authors.affiliation: Institut des Technologies Avancées en sciences du Vivant, Centre National de la Recherche Scientifique, Université Paul Sabatier, Université de Toulouse, 31106 Toulouse, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Russo
authors.affiliation: CELENYS, 76000 Rouen, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Vidal
authors.affiliation: CELENYS, 76000 Rouen, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Demange
authors.affiliation: CELENYS, 76000 Rouen, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Pannetier
authors.affiliation: CELENYS, 76000 Rouen, France.
authors.forename: Zied
authors.initials: Z
authors.lastname: Souguir
authors.affiliation: IMACTIV-3D, Centre Pierre Potier, 31106 Toulouse, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Lagarde
authors.affiliation: Institut des Technologies Avancées en sciences du Vivant, Centre National de la Recherche Scientifique, Université Paul Sabatier, Université de Toulouse, 31106 Toulouse, France; Centre Hospitalier Universitaire de Toulouse, 31059 Toulouse, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Ducommun
authors.affiliation: Institut des Technologies Avancées en sciences du Vivant, Centre National de la Recherche Scientifique, Université Paul Sabatier, Université de Toulouse, 31106 Toulouse, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Lobjois
keywords: 3D matrix; 3D models; automatic image quantification; microscopy; preclinical drug evaluation