Abstract
TRAIL-induced apoptosis is inhibited in GSCs. In this study, we investgated whether or not the widely used chemotherapeutic agent-TMZ can sensitize TRAIL treatment in GSCs, related mechanism was investigated in cultured glioma stem cells (GSCs) and primary glioma cells (PGCs) from patients. We found that the expression of c-Fas-associated death domain-like interleukin 1-converting enzyme-like inhibitory protein long and short isoforms (c-FLIPL and c-FLIPS, respectively) was significantly higher in GSCs than in PGCs, and was associated with greater tolerance to TRAIL treatment in the former. Application of the chemotherapeutic drug temozolomide (TMZ) induced the upregulation of casitas B-lineage lymphoma(c-Cbl) and downregulation of c-FLIPL and c-FLIPS expression in GSCs, and when combined with TRAIL promoted GSC apoptosis. These results suggest that combination therapy with TMZ and TRAIL may have clinical applicability for glioma treatment.
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