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    Characterization of carfilzomib-resistant non-small cell lung cancer cell lines.

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    Name:
    CFZ Resistant Cells manuscript ...
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    Description:
    Final Accepted Manuscript
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    Author
    Hanke, Neale T
    Imler, Elliot
    Marron, Marilyn T
    Seligmann, Bruce E
    Garland, Linda L
    Baker, Amanda F
    Affiliation
    Univ Arizona, Ctr Canc, Coll Med, Tucson, AZ 85721 USA
    Issue Date
    2018-07
    Keywords
    Carfilzomib
    Cross-resistance
    Drug resistance
    Lung cancer
    Non-small cell lung cancer
    Pgp
    Proteasome inhibitor
    
    Metadata
    Show full item record
    Publisher
    SPRINGER
    Citation
    Hanke, N. T., Imler, E., Marron, M. T., Seligmann, B. E., Garland, L. L., & Baker, A. F. (2018). Characterization of carfilzomib-resistant non-small cell lung cancer cell lines. Journal of cancer research and clinical oncology, 144(7), 1317-1327.
    Journal
    Journal of Cancer Research and Clinical Oncology
    Rights
    © Springer-Verlag GmbH Germany, part of Springer Nature 2018
    Collection Information
    This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
    Abstract
    We previously showed that carfilzomib (CFZ) has potent anti-proliferative and cytotoxic activity in a broad range of lung cancer cell lines. Here we investigate possible mechanisms of CFZ acquired resistance in lung cancer cell lines. CFZ-resistant non-small cell lung cancer (NSCLC) cell lines were developed by exposing A549 and H520 cells to stepwise increasing concentrations of CFZ. Resistance to CFZ and cross-resistance to bortezomib and other chemotherapy drugs was measured using the MTT assay. Cytotoxicity to CFZ was determined using a CytoTox assay. Western blot was used to measure apoptosis, autophagy, and drug efflux transporter-related proteins. Quantitative targeted whole transcriptome sequencing and quantitative RT-PCR was used to measure gene expression. Flow cytometry was used to analyze intracellular accumulation of doxorubicin. The CFZ IC Upregulation of Pgp appears to be an important, but not the only, mechanism of CFZ resistance in NSCLC cell lines.
    Note
    12 month embargo; published online 15 May 2018
    ISSN
    1432-1335
    PubMed ID
    29766327
    DOI
    10.1007/s00432-018-2662-0
    Version
    Final accepted manuscript
    Sponsors
    Onyx Pharmaceuticals, Inc.; Basic/Clinical Translational Partnership Pilot Grant award from the Arizona Cancer Center Support Grant [P30CA023074]; Basic/Clinical Translational Partnership Pilot Grant award from National Cancer Institute (NCI) [P30CA023074]
    Additional Links
    https://link-springer-com.ezproxy2.library.arizona.edu/article/10.1007/s00432-018-2662-0
    ae974a485f413a2113503eed53cd6c53
    10.1007/s00432-018-2662-0
    Scopus Count
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    UA Faculty Publications

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