In vivo, TRAIL delivered by MSCs was able to counteract tumor progression in two orthotopic models of Ewing sarcoma, associated with caspase activation, indicating that a cell-based delivery of a potent apoptosis-inducing factor could be relevant in EWS.
Cell viability experiments [3'[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis(4-methoxy-6-nitro-)benzene sulfonic acid hydrate (XTT) assay] showed that 4 of the 7 ES cell lines were resistant to TRAIL.
The sensitivity of osteosarcoma and Ewing's sarcoma cell lines to TRAIL was investigated in vitro by determining TRAIL receptor expression together with TRAIL effects on cell viability and apoptosis.
To our knowledge, this is the first report showing that interferon/cytokine combinations are able to induce TRAIL gene expression and TRAIL protein synthesis and secretion in Ewing sarcoma-derived cells.
Combined treatment using IFNgamma with TRAIL, APO1, TNFalpha or cytotoxic drugs cooperated to trigger apoptosis in various resistant tumor cell lines derived from Ewing tumor, neuroblastoma or medulloblastoma, while single agents exerted only a minimal effect.