Characterization of carfilzomib-resistant non-small cell lung cancer cell lines.
AuthorHanke, Neale T
Marron, Marilyn T
Seligmann, Bruce E
Garland, Linda L
Baker, Amanda F
AffiliationUniv Arizona, Ctr Canc, Coll Med, Tucson, AZ 85721 USA
Non-small cell lung cancer
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CitationHanke, 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 2018
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AbstractWe 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.
Note12 month embargo; published online 15 May 2018
VersionFinal accepted manuscript
SponsorsOnyx 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]