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

Abstract 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

MOESM1 of Testing ATRA and MEK inhibitor PD0325901 effectiveness in a nude mouse model for human MPNST xenografts

Additional file 1. Mean tumor volumes. Description of data: Mean volumes of transplanted MPNST (mmÂł) of two treatment groups (mice treated with ATRA and with MEKi) and of placebo group. Tumors were measured from day 7 until day 68 post transplantation. Treatment started at day 42. Average volumes and standard deviation over the whole group per day as well as difference of volumes between day 42 and 68 are given