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Testing ATRA and MEK inhibitor PD0325901 effectiveness in a nude mouse model for human MPNST xenografts

Lookup NU author(s): Monique Zangarini, Philip Berry, Professor Gareth Veal

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2018 The Author(s). Objective: Malignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas characterized by high recurrence rates and early metastases. These tumors arise more frequently within neurofibromatosis type 1 (NF1) and present with resistance during standard chemotherapy leading to increased mortality and morbidity in those patients. In vitro all-trans retinoic acid (ATRA) and MEK inhibitors (MEKi) were shown to inhibit tumor proliferation, especially when applied in combination. Therefore, we established a nude mouse model to investigate if treatment of xenografts derived from NF1 associated S462 and T265 MPNST cells respond to ATRA and the MEKi PD0325901. Results: We demonstrated that human NF1 associated MPNST derived from S462 but not T265 cells form solid subcutaneous tumors in Foxn1 nude mice but not in Balb/c, SHO or Shorn mice. We verified a characteristic staining pattern of human MPNST xenografts by immunohistochemistry. Therapeutic effects of ATRA and/or MEKi PD0325901 on growth of S462 MPNST xenografts in Foxn1 nude mice were not demonstrated in vitro, as we did not observe significant suppression of MPNST growth compared with placebo treatment.


Publication metadata

Author(s): Fischer-Huchzermeyer S, Chikobava L, Stahn V, Zangarini M, Berry P, Veal GJ, Senner V, Mautner VF, Harder A

Publication type: Article

Publication status: Published

Journal: BMC Research Notes

Year: 2018

Volume: 11

Issue: 1

Online publication date: 28/07/2018

Acceptance date: 20/07/2018

Date deposited: 13/08/2018

ISSN (electronic): 1756-0500

Publisher: BioMed Central Ltd.

URL: https://doi.org/10.1186/s13104-018-3630-0

DOI: 10.1186/s13104-018-3630-0


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