Characterization of carfilzomib-resistant non-small cell lung cancer cell lines.
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CFZ Resistant Cells manuscript ...
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Final Accepted Manuscript
Author
Hanke, Neale TImler, Elliot
Marron, Marilyn T
Seligmann, Bruce E
Garland, Linda L
Baker, Amanda F
Affiliation
Univ Arizona, Ctr Canc, Coll Med, Tucson, AZ 85721 USAIssue Date
2018-07Keywords
CarfilzomibCross-resistance
Drug resistance
Lung cancer
Non-small cell lung cancer
Pgp
Proteasome inhibitor
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SPRINGERCitation
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.Rights
© Springer-Verlag GmbH Germany, part of Springer Nature 2018Collection 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 2018ISSN
1432-1335PubMed ID
29766327Version
Final accepted manuscriptSponsors
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/s00432-018-2662-0ae974a485f413a2113503eed53cd6c53
10.1007/s00432-018-2662-0