Open AccessNovel 3‐D cell culture system for in vitro evaluation of anticancer drugs under anchorage‐independent conditions
Author(s) -
Aihara Ayako,
Abe Natsuki,
Saruhashi Koichiro,
Kanaki Tatsuro,
Nishino Taito
Publication year - 2016
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13095
Subject(s) - cell culture , in vivo , cell growth , in vitro , cell , receptor , epidermal growth factor , cancer cell , cancer research , pharmacology , chemistry , biology , microbiology and biotechnology , cancer , medicine , biochemistry , genetics
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 ( FP 001), as the most potent polymer. FP 001 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 FP 001‐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 SKOV 3 ovarian carcinoma cells under anchorage‐independent conditions with FP 001. Consistent with this result, the cells grown with FP 001 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 FP 001 will be of value in the development of useful technologies for anticancer drug discovery.