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

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.
AuthorsWei Jiang, Claudia Schnabel, Melanie Spyra, Victor-F Mautner, Reinhard E Friedrich, Christian Hagel, Paul W Manley, Lan Kluwe
JournalJournal of neuro-oncology (J Neurooncol) Vol. 116 Issue 2 Pg. 231-6 (Jan 2014) ISSN: 1573-7373 [Electronic] United States
PMID24173684 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Annexin A5
  • Enzyme Inhibitors
  • Pyrimidines
  • Thy-1 Antigens
  • Collagenases
  • nilotinib
Topics
  • Annexin A5 (metabolism)
  • Apoptosis (drug effects, genetics)
  • Cell Proliferation (drug effects)
  • Collagenases (metabolism)
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors (pharmacology)
  • Humans
  • Nerve Sheath Neoplasms (genetics, pathology)
  • Neurofibromatosis 1 (genetics, pathology)
  • Pyrimidines (pharmacology)
  • Schwann Cells (drug effects)
  • Thy-1 Antigens (metabolism)
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

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