title: A novel 96-well multielectrode array based impedimetric monitoring platform for comparative drug efficacy analysis on 2D and 3D brain tumor cultures.
abstract: Aggressive cancer entities like neuroblastoma and glioblastoma multiforme are still difficult to treat and have discouraging prognosis in malignant stage. Since each tumor has its own characteristics concerning the sensitivity towards different chemotherapeutics and moreover, can obtain resistance, the development of novel chemotherapeutics with a broad activity spectrum, high efficacy and minimum side effects is a continuous process. Sophisticated in vitro assays for comprehensive prediction of in vivo drug efficacy and side effects represent an actual bottleneck in the drug development process. In this context, we developed a novel in vitro 2D and 3D multiwell-multielectrode device for drug efficacy monitoring based on direct real-time impedance spectroscopy measurement in combination with our unique 96-well multielectrode arrays and microcavity arrays. For demonstration, we used three neuro- and glioblastoma cell lines that were cultured as monolayer and multicellular tumor spheroids for recapitulating in vivo conditions. Using our novel 96-well multielectrode array based system it was possible to detect time and concentration dependent responses concerning treatment with doxorubicin, etoposide and vincristine. While all tested chemotherapeutics revealed high potency for apoptosis induction in neuroblastoma cells, etoposide was ineffective for glioblastoma cell lines. Determination of IC50 values allowed us to compare drug efficacy in 2D and 3D culture models and moreover, revealed chemotherapeutic and tumor cell line specific activity patterns. These pharmacokinetic patterns are of great interest in the context of preclinical drug development. Thus, impedance spectroscopy based monitoring systems could be used for the fast in vitro based in vivo prediction of novel anti-tumor drugs.
authors.affiliation: Center for Biotechnology and Biomedicine (BBZ), University of Leipzig, Division of Molecular Biological-Biochemical Processing Technology, Deutscher Platz 5, 04103 Leipzig, Germany.
authors.forename: Marie
authors.initials: M
authors.lastname: Eichler
authors.affiliation: Center for Biotechnology and Biomedicine (BBZ), University of Leipzig, Division of Molecular Biological-Biochemical Processing Technology, Deutscher Platz 5, 04103 Leipzig, Germany.
authors.forename: Heinz-Georg
authors.initials: HG
authors.lastname: Jahnke
authors.affiliation: Center for Biotechnology and Biomedicine (BBZ), University of Leipzig, Division of Molecular Biological-Biochemical Processing Technology, Deutscher Platz 5, 04103 Leipzig, Germany.
authors.forename: Dana
authors.initials: D
authors.lastname: Krinke
authors.affiliation: Center for Biotechnology and Biomedicine (BBZ), University of Leipzig, Division of Molecular Biological-Biochemical Processing Technology, Deutscher Platz 5, 04103 Leipzig, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Müller
authors.affiliation: Center for Biotechnology and Biomedicine (BBZ), University of Leipzig, Division of Molecular Biological-Biochemical Processing Technology, Deutscher Platz 5, 04103 Leipzig, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Schmidt
authors.affiliation: Center for Biotechnology and Biomedicine (BBZ), University of Leipzig, Division of Molecular Biological-Biochemical Processing Technology, Deutscher Platz 5, 04103 Leipzig, Germany.
authors.forename: Ronny
authors.initials: R
authors.lastname: Azendorf
authors.affiliation: Center for Biotechnology and Biomedicine (BBZ), University of Leipzig, Division of Molecular Biological-Biochemical Processing Technology, Deutscher Platz 5, 04103 Leipzig, Germany. Electronic address: andrea.robitzki@bbz.uni-leipzig.de.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Robitzki
mesh_terms: D017209:Apoptosis; D015374:Biosensing Techniques; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D058266:Dielectric Spectroscopy; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D018874:Spheroids, Cellular; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin
keywords: 3D brain tumor models; 96-well-multielectrode array; Drug efficacy monitoring; Impedance spectroscopy; Microcavity array