The traditional method for studying
cancer in vitro is to grow immortalized
cancer cells in two-dimensional monolayers on
plastic. However, many cellular features are impaired in these artificial conditions, and large changes in gene expression compared to
tumors have been reported. Three-dimensional cell culture models have become increasingly popular and are suggested to be better models than two-dimensional monolayers due to improved cell-to-cell contact and structures that resemble in vivo architecture. The aim of this study was to develop a simple high-throughput three-dimensional
drug screening method and to compare
drug responses in JIMT1
breast cancer cells when grown in two dimensions, in poly(2-hydroxyethyl methacrylate) induced anchorage-independent three-dimensional models, and in
Matrigel three-dimensional cell culture models. We screened 102 compounds with multiple concentrations and
biological replicates for their effects on cell proliferation. The cells were either treated immediately upon plating, or they were allowed to grow in three-dimensional cultures for 4 days before the
drug treatment. Large variations in
drug responses were observed between the models indicating that comparisons of culture model-influenced
drug sensitivities cannot be made based on the effects of a single
drug. However, we show with the 63 most prominent drugs that, in general, JIMT1 cells grown on
Matrigel were significantly more sensitive to drugs than cells grown in two-dimensional cultures, while the responses of cells grown in poly(2-hydroxyethyl methacrylate) resembled those of the two-dimensional cultures. Furthermore, comparing the gene expression profiles of the cell culture models to xenograft
tumors indicated that cells cultured in
Matrigel and as xenografts most closely resembled each other. In this study, we also suggest that three-dimensional cultures can provide a platform for systematic experimentation of larger compound collections in a high-throughput mode and be used as alternatives to traditional two-dimensional screens for better comparability to the in vivo state.