TNF-related apoptosis-inducing ligand (TRAIL) is a potent inducer of apoptosis in adult malignant glioma and various other human solid tumor models but not in normal tissues.
In the present study we have utilized a panel of seven cell lines derived from human malignant gliomas to characterize molecular pathways through which FasL and TRAIL induce apoptosis in sensitive glioma cells and the mechanisms of resistance in cell lines which survive the death stimuli.
It was the aim of our study to determine which genomic alterations in malignant gliomas modulate the sensitivity to chemotherapy or cytotoxic cytokines such as CD95 ligand (CD95L) or Apo2L/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL).
Our data indicate that Bcl-2 and Bcl-xL play fundamental roles in TRAIL resistance of malignant glioma and suggest that using TRAIL or agonistic TRAIL receptor antibodies in combination with BH3 mimetics may represent a promising approach to reactivate apoptosis in therapy-resistant high grade gliomas.
To investigate the molecular basis of an experimental combination therapy for malignant gliomas with TRAIL and Troglitazone, we investigated the Troglitazone-induced signaling cascades and the expression of TRAIL receptors and FLIP in malignant gliomas.