Increased malignant behavior in neuroblastoma cells with acquired multi-drug resistance does not depend on P-gp expression

  • Authors:
    • Rouslan Kotchetkov
    • Pablo Hernáiz Driever
    • Jaroslav Cinatl
    • Martin Michaelis
    • Jana Karaskova
    • Roman Blaheta
    • Jeremy A. Squire
    • Andreas Von Deimling
    • Jussi Moog
    • Jindrich Cinatl
  • View Affiliations

  • Published online on: October 1, 2005     https://doi.org/10.3892/ijo.27.4.1029
  • Pages: 1029-1037
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Abstract

Acquisition of P-gp-mediated multidrug-resistance does not always correlate with observed malignant behavior of NB. To characterize alterations accompanying development of multidrug-resistance in NB we established two neuroblastoma cell sublines resistant to vincristine (UKF-NB-3rVCR10) and doxorubicin (UKF-NB-3rDOX20). UKF-NB-3rVCR10 and UKF-NB-3rDOX20 overexpressed functional P-gp and developed an increased malignant phenotype: presented constitutive phosphorylation of AKT, resistance to γ-irradiation, and had increased survival in serum-free medium. Inhibition of P-gp restored chemosensitivity but did not affect increased survival in serum-free medium and sensitivity to γ-irradiation. Inhibition of AKT had no influence on chemoresistance but restored sensitivity to serum starvation. Both resistant cell lines acquired additional chromosomal changes. UKF-NB-3rVCR10 cells acquired a missense P53 mutation in exon 5, an increased MYCN amplification, an enhanced adhesion to endothelium, a decreased NCAM expression, a distinctly higher clonogenicity, and an increased in vivo tumorigenicity. We conclude that acquisition of increased malignant behavior in neuroblastoma occurs concomitantly with multidrug-resistance and is P-gp-independent.

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October 2005
Volume 27 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Kotchetkov, R., Driever, P.H., Cinatl, J., Michaelis, M., Karaskova, J., Blaheta, R. ... Cinatl, J. (2005). Increased malignant behavior in neuroblastoma cells with acquired multi-drug resistance does not depend on P-gp expression. International Journal of Oncology, 27, 1029-1037. https://doi.org/10.3892/ijo.27.4.1029
MLA
Kotchetkov, R., Driever, P. H., Cinatl, J., Michaelis, M., Karaskova, J., Blaheta, R., Squire, J. A., Von Deimling, A., Moog, J., Cinatl, J."Increased malignant behavior in neuroblastoma cells with acquired multi-drug resistance does not depend on P-gp expression". International Journal of Oncology 27.4 (2005): 1029-1037.
Chicago
Kotchetkov, R., Driever, P. H., Cinatl, J., Michaelis, M., Karaskova, J., Blaheta, R., Squire, J. A., Von Deimling, A., Moog, J., Cinatl, J."Increased malignant behavior in neuroblastoma cells with acquired multi-drug resistance does not depend on P-gp expression". International Journal of Oncology 27, no. 4 (2005): 1029-1037. https://doi.org/10.3892/ijo.27.4.1029