Open Access

Resistance to nanoparticle albumin-bound paclitaxel is mediated by ABCB1 in urothelial cancer cells

  • Authors:
    • Stefan Vallo
    • Raoul Köpp
    • Martin Michaelis
    • Florian Rothweiler
    • Georg Bartsch
    • Maximilian P. Brandt
    • Kilian M. Gust
    • Felix Wezel
    • Roman A. Blaheta
    • Axel Haferkamp
    • Jindrich Cinatl
  • View Affiliations

  • Published online on: April 5, 2017     https://doi.org/10.3892/ol.2017.5986
  • Pages: 4085-4092
  • Copyright: © Vallo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Nanoparticle albumin‑bound (nab)-paclitaxel appears to exhibit better response rates in patients with metastatic urothelial cancer of the bladder whom are pretreated with nab-paclitaxel compared with conventional paclitaxel. Paclitaxel may induce multidrug resistance in patients with cancer, while the mechanisms of resistance against paclitaxel are manifold. These include reduced function of pro‑apoptotic proteins, mutations of tubulin and overexpression of the drug transporter adenosine 5'‑triphosphate‑binding cassette transporter subfamily B, member 1 (ABCB1). To evaluate the role of ABCB1 in nab‑paclitaxel resistance in urothelial cancer cells, the bladder cancer cell lines T24 and TCC‑SUP, as well as sub‑lines with acquired resistance against gemcitabine (T24rGEMCI20 and TCC‑SUPrGEMCI20) and vinblastine (T24rVBL20 and TCC‑SUPrVBL20) were examined. For the functional inhibition of ABCB1, multi-tyrosine kinase inhibitors with ABCB1‑inhibiting properties, including cabozantinib and crizotinib, were used. Additional functional assessment was performed with cell lines stably transduced with a lentiviral vector encoding for ABCB1, and protein expression was determined by western blotting. It was indicated that cell lines overexpressing ABCB1 exhibited similar resistance profiles to nab‑paclitaxel and paclitaxel. Cabozantinib and crizotinib sensitized tumor cells to nab‑paclitaxel and paclitaxel in the same dose‑dependent manner in cell lines overexpressing ABCB1, without altering the downstream signaling of tyrosine kinases. These results suggest that the overexpression of ABCB1 confers resistance to nab‑paclitaxel in urothelial cancer cells. Additionally, small molecules may overcome resistance to anticancer drugs that are substrates of ABCB1.
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June-2017
Volume 13 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Copy and paste a formatted citation
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Spandidos Publications style
Vallo S, Köpp R, Michaelis M, Rothweiler F, Bartsch G, Brandt MP, Gust KM, Wezel F, Blaheta RA, Haferkamp A, Haferkamp A, et al: Resistance to nanoparticle albumin-bound paclitaxel is mediated by ABCB1 in urothelial cancer cells. Oncol Lett 13: 4085-4092, 2017.
APA
Vallo, S., Köpp, R., Michaelis, M., Rothweiler, F., Bartsch, G., Brandt, M.P. ... Cinatl , J. (2017). Resistance to nanoparticle albumin-bound paclitaxel is mediated by ABCB1 in urothelial cancer cells. Oncology Letters, 13, 4085-4092. https://doi.org/10.3892/ol.2017.5986
MLA
Vallo, S., Köpp, R., Michaelis, M., Rothweiler, F., Bartsch, G., Brandt, M. P., Gust, K. M., Wezel, F., Blaheta, R. A., Haferkamp, A., Cinatl , J."Resistance to nanoparticle albumin-bound paclitaxel is mediated by ABCB1 in urothelial cancer cells". Oncology Letters 13.6 (2017): 4085-4092.
Chicago
Vallo, S., Köpp, R., Michaelis, M., Rothweiler, F., Bartsch, G., Brandt, M. P., Gust, K. M., Wezel, F., Blaheta, R. A., Haferkamp, A., Cinatl , J."Resistance to nanoparticle albumin-bound paclitaxel is mediated by ABCB1 in urothelial cancer cells". Oncology Letters 13, no. 6 (2017): 4085-4092. https://doi.org/10.3892/ol.2017.5986