Sensitization of human glioblastomas to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) by NF-kappaB inhibitors

Abstract

Glioblastoma is the most malignant form of primary brain tumor in adults, with no effective therapy and a low survival rate. TRAIL is a member of the TNF family, which selectively induces apoptosis in certain neoplastic cells, but not normal cells. In this study, we investigated the sensitivity of 7 human glioblastoma cell lines to TRAIL and the expression in them of TRAIL receptors. TRAIL exhibited significant cytotoxicity in 5 of 7 glioma cell lines. These glioblastoma cell lines expressed TRAIL‐R2, but not TRAIL‐R1, R3, or R4. However, no correlation was observed between the TRAIL sensitivity and the TRAIL‐R2 expression level, suggesting that there is an additional determinant of TRAIL sensitivity. Treatments with NF‐κB inhibitors, such as LLnL, MG132, and SN50, significantly increased the sensitivity of glioma cells to TRAIL. These results suggested that activation of NF‐κB is a protective mechanism against TRAIL‐induced cell death in some glioma cells, and thus NF‐κB inhibitors may be useful to improve the clinical treatment of glioblastoma with TRAIL.