Combination treatment with VPA and MSCs-TRAIL could increase anti-tumor effects against intracranial glioma

Human bone marrow-derived mesenchymal stem cells secreting tumor necrosis factor-related apoptosis-inducing ligand (MSCs-TRAIL) have demonstrated effective anti-tumor activity against various tumors including lung, pancreatic and prostate tumors, although several tumor types are not responsive. In such case, other reagents may decrease tumor growth via TRAIL-mediated cell death. The present study aimed to examine the effectiveness of valproic acid (VPA) in enhancing the efficacy of TRAIL, which was delivered using MSCs. Moreover, the present study examined the induced tumor tropism of MSCs via cell viability and migration assays. Combination treatment with VPA and MSCs-TRAIL enhanced the glioma therapeutic effect by increasing death receptor 5 and caspase activation. Migration assays identified increased MSC migration in VPA and MSCs-TRAIL-treated glioma cells and in the tumor site in glioma-bearing mice compared with VPA or MSC-TRAIL treatment alone. In vivo experiments demonstrated that MSC-based TRAIL gene delivery to VPA-treated tumors had greater therapeutic efficacy compared with treatment with each agent alone. These findings suggested that VPA treatment increased the therapeutic efficacy of MSC-TRAIL via TRAIL-induced apoptosis and enhanced tropism of MSCs, which may offer a useful strategy for tumor gene therapy.