Effect of triptolide on malignant peripheral nerve sheath tumours in vitro and in vivo

Abstract

OBJECTIVE: Malignant peripheral nerve sheath tumours (MPNSTs) are invasive, hard-to-treat, soft tissue sarcomas. In this study, in vitro and in vivo effects of triptolide were investigated using human MPNST cell lines. METHODS: Cultured STS-26T and ST88-14 cells were treated with 0 - 100 ng/ml triptolide (for determination of cell proliferation by sulphorhodamine B assay), with 12.5 ng/ml or 25 ng/ml triptolide (for analysis of caspase activity, effects on apoptotic pathway intermediates [by Western blots and flow cytometry], and for measurement of vascular endothelial growth factor [VEGF] and epidermal growth factor receptor [EGFR] levels by enzyme-linked immunosorbent assay). A xenograft model was established by injection of STS-26T cells into nude mice, and the effects of 250 μg/kg triptolide on tumour growth and apoptosis were compared with controls. RESULTS: Triptolide significantly inhibited cell proliferation and induced apoptosis in vitro, through activation of caspases, in a dose- and time-dependent manner; VEGF and EGFR levels were suppressed. In vivo, triptolide inhibited the growth of STS-26T xenografts and reduced apoptosis. CONCLUSION: Triptolide may have a therapeutic benefit in MPNST treatment. © SAGE Publications Ltd 2012.