Evaluation of Combination Treatment Effect With TRAIL-secreting Mesenchymal Stem Cells and Compound C Against Glioblastoma

Abstract

BACKGROUND/AIM: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis of cancer cells and, when used in combination with other anticancer drugs, is regarded as an effective strategy for anticancer treatment. In this study, we investigated the efficacy of combination treatment with TRAIL-secreting human mesenchymal stem cells (MSC-TRAIL) and compound C, an AMP-activated protein kinase (AMPK inhibitor), on glioblastoma. MATERIALS AND METHODS: The anticancer effect using MSC-TRAIL and compound C on glioma was evaluated in vitro and on in vivo models. RESULTS: Combination treatment of MSC-TRAIL and compound C increased apoptosis by enhancing expression of B-cell lymphoma 2 (BCL2)-associated X protein (BAX) and reducing that of anti-apoptotic proteins cellular FLICE-inhibitory protein (FLIP), X-linked inhibitor of apoptosis (XIAP), and BCL2 in glioma. In addition, MSC-TRAIL and compound C combination increased caspase-3 cleavage and apoptotic cells in a mouse glioma model compared with the group treated with the agents alone. CONCLUSION: Our results suggest that MSC-TRAIL and compound C are a novel combination for treatment of glioma.