Abstract 844: Peroxisome proliferator-activated receptor γ agonists abrogate tumor invasion and promote TRAIL-induced apoptosis in malignant glioma.

Abstract

Abstract Glioblastoma multiforme is the most common brain tumors and have a worse prognosis, so it is needed to develop effective treatments. Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists, including 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and synthetic ligands, troglitazone and rosiglitazone, are known to sensitize tumor cells to apoptosis via various molecular mechanisms. In this study, we investigated the therapeutic potentials of combined treatment with PPAR-γ agonists and TRAIL in TRAIL-resistant astrocytoma cells. TRAIL alone and each PPAR-γ agonist exhibited no cytotoxic effects; while the pre-incubation with PPAR-γ agonists enhanced dramatically TRAIL-induced cell death, which was abrogated by a broad spectrum caspase inhibitor, z-VAD-fmk. And also, the combined treatment with PPAR-γ agonists and TRAIL increased the enzymatic activity of caspase-3. These results indicate that PPAR-γ agonists might promote TRAIL-mediated apoptosis by modulating the caspase activity. In addition, the expression of anti-apoptotic proteins including FLIP, Bcl-2, Bcl-xL and XIAP was suppressed by the combined treatment. Besides the cytotoxic effect, treatment with PPAR-γ agonists significantly inhibited glioma invasion in vitro and in vivo. These results collectively suggest that PPAR-γ agonists may provide a promising strategy to treat malignant glioma. Citation Format: Kyungsun Choi, Kyuha Chong, Jungwhoi Lee, Hojun Choi, Chulhee Choi. Peroxisome proliferator-activated receptor γ agonists abrogate tumor invasion and promote TRAIL-induced apoptosis in malignant glioma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 844. doi:10.1158/1538-7445.AM2013-844