Journal of Neuro-Oncology

, Volume 116, Issue 2, pp 231–236

Efficacy and selectivity of nilotinib on NF1-associated tumors in vitro

  • Wei Jiang
  • Claudia Schnabel
  • Melanie Spyra
  • Victor-F Mautner
  • Reinhard E. Friedrich
  • Christian Hagel
  • Paul W. Manley
  • Lan Kluwe
Laboratory Investigation

DOI: 10.1007/s11060-013-1295-z

Cite this article as:
Jiang, W., Schnabel, C., Spyra, M. et al. J Neurooncol (2014) 116: 231. doi:10.1007/s11060-013-1295-z

Abstract

Neurofibromatosis type 1 is a tumor suppressor gene disorder which predisposes patients to cutaneous neurofibromas, plexiform neurofibromas (PNFs) and malignant peripheral nerve sheath tumors (MPNSTs) among other neoplasias and manifestation. In this study, we examined the efficiency of nilotinib on PNF-derived Schwann cells and on cells of established MPNST lines in vitro. Nilotinib treatment for 10 days led to decreased proliferation, viability and vitality of the cells with 50 % inhibitory concentration (IC50) for proliferation varying from 3.1 to 9.0 μM. We further addressed selectivity of the drug for tumor cells by simultaneously examining its efficacy on tumor cells (Schwann cells) and non-tumor cells (fibroblasts) from the same tumor. For four out of the six PNFs studied, IC50 was lower in Schwann cells than in fibroblasts for all parameters measured (proliferation, vitality and viability), indicating good drug selectivity. In addition, nilotinib induced apoptosis and suppressed collagenase activity. Our results suggest that nilotinib may provide a treatment option for some PNFs and MPNSTs and our in vitro model of comparative treatment on tumor and non-tumor cells may provide a prototype of preclinical drug screening system toward personalized treatment.

Keywords

Neurofibromatosis type 1 Plexiform neurofibroma Malignant peripheral nerve sheath tumors Nilotinib Drug selectivity 

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Wei Jiang
    • 1
  • Claudia Schnabel
    • 1
  • Melanie Spyra
    • 1
  • Victor-F Mautner
    • 1
  • Reinhard E. Friedrich
    • 2
  • Christian Hagel
    • 3
  • Paul W. Manley
    • 4
  • Lan Kluwe
    • 1
    • 2
  1. 1.Laboratory for Tumor Genetics, Department of NeurologyUniversity Medical Center Hamburg-EppendorfHamburgGermany
  2. 2.Department of Maxillofacial SurgeryUniversity Medical Center Hamburg-EppendorfHamburgGermany
  3. 3.Institute of NeuropathologyUniversity Medical Center Hamburg-EppendorfHamburgGermany
  4. 4.Novartis Institute of Biomedical ResearchBaselSwitzerland

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