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

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Efficacy and selectivity of nilotinib on NF1-associated tumors in vitro. / Wei, Jiang; Schnabel, Claudia; Spyra, Melanie; Mautner, Viktor-Felix; Friedrich, Reinhard E; Hagel, Christian; Manley, Paul W; Kluwe, Lan.

In: J NEURO-ONCOL, Vol. 116, No. 2, 01.01.2014, p. 231-6.

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@article{0d2effe82bed4bd6ab980f5e74efba5f,
title = "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.",
author = "Jiang Wei and Claudia Schnabel and Melanie Spyra and Viktor-Felix Mautner and Friedrich, {Reinhard E} and Christian Hagel and Manley, {Paul W} and Lan Kluwe",
year = "2014",
month = jan,
day = "1",
doi = "10.1007/s11060-013-1295-z",
language = "English",
volume = "116",
pages = "231--6",
journal = "J NEURO-ONCOL",
issn = "0167-594X",
publisher = "Kluwer Academic Publishers",
number = "2",

}

RIS

TY - JOUR

T1 - Efficacy and selectivity of nilotinib on NF1-associated tumors in vitro

AU - Wei, Jiang

AU - Schnabel, Claudia

AU - Spyra, Melanie

AU - Mautner, Viktor-Felix

AU - Friedrich, Reinhard E

AU - Hagel, Christian

AU - Manley, Paul W

AU - Kluwe, Lan

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

U2 - 10.1007/s11060-013-1295-z

DO - 10.1007/s11060-013-1295-z

M3 - SCORING: Journal article

C2 - 24173684

VL - 116

SP - 231

EP - 236

JO - J NEURO-ONCOL

JF - J NEURO-ONCOL

SN - 0167-594X

IS - 2

ER -