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

Kotchetkov, Rouslan, Driever, Pablo Hernáiz, Cinatl, Jaroslav, Michaelis, Martin, Karaskova, Jana, Blaheta, Roman A., Squire, Jeremy A., Von Deimling, Andreas, Moog, Jussi, Cinatl, Jindrich and others. (2005) Increased malignant behavior in neuroblastoma cells with acquired multi-drug resistance does not depend on P-gp expression. International Journal of Oncology, 27 (4). pp. 1029-37. ISSN 1019-6439. (doi:10.3892/ijo.27.4.1029) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Official URL
http://dx.doi.org/10.3892/ijo.27.4.1029

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 gamma-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 gamma-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.

Item Type: Article
DOI/Identification number: 10.3892/ijo.27.4.1029
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Martin Michaelis
Date Deposited: 05 Jun 2013 20:40 UTC
Last Modified: 29 May 2019 10:14 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/34107 (The current URI for this page, for reference purposes)
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