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Dissecting multi drug resistance in head and neck cancer cells using multicellular tumor spheroids
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology.
Natl Inst Technol Durgapur, India.
Lund Univ, Sweden.
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 20066Article in journal (Refereed) Published
Abstract [en]

One of the hallmarks of cancers is their ability to develop resistance against therapeutic agents. Therefore, developing effective in vitro strategies to identify drug resistance remains of paramount importance for successful treatment. One of the ways cancer cells achieve drug resistance is through the expression of efflux pumps that actively pump drugs out of the cells. To date, several studies have investigated the potential of using 3-dimensional (3D) multicellular tumor spheroids (MCSs) to assess drug resistance; however, a unified system that uses MCSs to differentiate between multi drug resistance (MDR) and non-MDR cells does not yet exist. In the present report we describe MCSs obtained from post-diagnosed, pre-treated patient-derived (PTPD) cell lines from head and neck squamous cancer cells (HNSCC) that often develop resistance to therapy. We employed an integrated approach combining response to clinical drugs and screening cytotoxicity, monitoring real-time drug uptake, and assessing transporter activity using flow cytometry in the presence and absence of their respective specific inhibitors. The report shows a comparative response to MDR, drug efflux capability and reactive oxygen species (ROS) activity to assess the resistance profile of PTPD MCSs and two-imensional (2D) monolayer cultures of the same set of cell lines. We show that MCSs provide a robust and reliable in vitro model to evaluate clinical relevance. Our proposed strategy can also be clinically applicable for profiling drug resistance in cancers with unknown resistance profiles, which consequently can indicate benefit from downstream therapy.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019. Vol. 9, article id 20066
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:liu:diva-164057DOI: 10.1038/s41598-019-56273-6ISI: 000509327800012PubMedID: 31882620Scopus ID: 2-s2.0-85077332553OAI: oai:DiVA.org:liu-164057DiVA, id: diva2:1411013
Note

Funding Agencies|MIIC, PDF grant; Linkoping University, Sweden; EU H2020 Marie Sklodowska-Curie Individual Fellowship [706694]; European CommissionEuropean Commission Joint Research Centre; Wolfson College, University of CambridgeUniversity of Cambridge; MIIC Strategic Postdoc Grant; MIIC Seed Grant at Linkoping University (LiU), Sweden; Swedish Cancer SocietySwedish Cancer Society [2017/301]; County Council of Ostergotland; Research Funds of Linkoping University Hospital

Available from: 2020-03-02 Created: 2020-03-02 Last updated: 2020-04-27Bibliographically approved

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D´arcy, Padraig

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Azharuddin, MohammadRoberg, KarinD´arcy, PadraigHinkula, JormaPatra, Hirak Kumar
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