title: Novel 3-D cell culture system for in vitro evaluation of anticancer drugs under anchorage-independent conditions.
abstract: Anticancer drug discovery efforts have used 2-D cell-based assay models, which fail to forecast in vivo efficacy and result in a lower success rate of clinical approval. Recent 3-D cell culture models are expected to bridge the gap between 2-D and in vivo models. However, 3-D cell culture methods that are available for practical anticancer drug screening have not yet been fully attained. In this study, we screened several polymers for their ability to suspend cells or cell spheroids homogeneously in a liquid medium without changing the viscosity behavior, and identified gellan gum (FP001), as the most potent polymer. FP001 promoted cell dispersion in the medium and improved the proliferation of a wide range of cancer cell lines under low attachment conditions by inhibiting the formation of large-sized spheroids. In addition, cancer cells cultured with FP001-containing medium were more susceptible to inhibitors of epidermal growth factor (EGF) signaling than those cultured under attachment conditions. We also showed that ligands of the EGF receptor family clearly enhance proliferation of SKOV3 ovarian carcinoma cells under anchorage-independent conditions with FP001. Consistent with this result, the cells grown with FP001 showed higher EGF receptor content compared with cells cultured under attachment conditions. In conclusion, we developed a novel 3-D cell culture system that is available for high throughput screening of anticancer agents, and is suitable for evaluation of molecular-targeted anticancer drugs. Three-dimensional cell culture using FP001 will be of value in the development of useful technologies for anticancer drug discovery.
authors.affiliation: Biological Research Laboratories, Nissan Chemical Industries Ltd, Saitama, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Aihara
authors.affiliation: Biological Research Laboratories, Nissan Chemical Industries Ltd, Saitama, Japan.
authors.forename: Natsuki
authors.initials: N
authors.lastname: Abe
authors.affiliation: Material Research Laboratories, Nissan Chemical Industries Ltd, Chiba, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Saruhashi
authors.affiliation: Biological Research Laboratories, Nissan Chemical Industries Ltd, Saitama, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Kanaki
authors.affiliation: Biological Research Laboratories, Nissan Chemical Industries Ltd, Saitama, Japan.
authors.forename: Taito
authors.initials: T
authors.lastname: Nishino
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D055808:Drug Discovery; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004815:Epidermal Growth Factor; D066246:ErbB Receptors
keywords: 3-D cell culture; anticancer drugs; gellan gum; high throughput screening (HTS); spheroids