title: Development, validation and pilot screening of an in vitro multi-cellular three-dimensional cancer spheroid assay for anti-cancer drug testing.
abstract: It has been demonstrated that two-dimensional (2D) monolayer cancer cell proliferation assay for anti-cancer drug screening is a very artificial model and cannot represent the characteristics of three-dimensional (3D) solid tumors. The multi-cellular in vitro 3D tumor spheroid model is of intermediate complexity, and can provide a bridge to the gap between the complex in vivo tumors and simple in vitro monolayer cell cultures. In this study, a simple and cost-effective cancer 3D spheroid assay suitable for small molecule anti-cancer compound screening was developed, standardized and validated on H292 non-small lung cancer cell line. A pilot screening with this assay was performed utilizing a compound library consisting of 41 anti-cancer agents. The traditional 2D monolayer cell proliferation assay was also performed with the same cell line and compounds. A correlational study based on the IC(50) values from the 2D and 3D assays was conducted. There is low correlation with the two sets of biological data, suggesting the two screening methods provide different information regarding the potency of the tested drug candidates.
authors.affiliation: Department of Chemistry, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA.
authors.forename: Rati
authors.initials: R
authors.lastname: Lama
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Janine M
authors.initials: JM
authors.lastname: Naim
authors.forename: Jennifer
authors.initials: J
authors.lastname: Williams
authors.forename: Aimin
authors.initials: A
authors.lastname: Zhou
authors.forename: Bin
authors.initials: B
authors.lastname: Su
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007700:Kinetics; D017239:Paclitaxel / Q000737:chemistry / Q000633:toxicity; D018874:Spheroids, Cellular / Q000187:drug effects*; D013449:Sulfonamides / Q000737:chemistry / Q000633:toxicity; D050257:Tubulin Modulators / Q000633:toxicity; D014407:Tumor Cells, Cultured
chemical_list: C490492:ABT751; D000970:Antineoplastic Agents; D013449:Sulfonamides; D050257:Tubulin Modulators; D017239:Paclitaxel