Combined treatment using nonviral agent-mediated
enzyme/
prodrug therapy and
immunotherapy had been proposed as a powerful alternative method of
cancer therapy. The present study was aimed to evaluate the cytotoxicity in vitro and the therapeutic efficacy in vivo when the
cytosine deaminase/5-fluorocytosine (CD/5-FC) and
TNF-related apoptosis-inducing ligand (TRAIL) genes were jointly used against rat C6
glioma cells. The potency of the FA-
PEG-PEI used as a nonviral vector was tested in the FR-expressed C6
glioma cells and Wistar rats. The C6
glioma cells and animal model were treated by the combined application of FA-
PEG-PEI/pCD/5-FC and FA-
PEG-PEI/pTRAIL. The antitumor effect was evaluated by survival assays and
tumor volume. This study revealed a significant increase of cytotoxicity in vitro following the combined application of FA-
PEG-PEI/pCD/5-FC and FA-
PEG-PEI/pTRAIL treatments in C6
glioma cells. Animal studies showed a significant growth inhibition of the C6
glioma xenografts using the combined treatment. These results demonstrated that the combined treatment generated additive cytotoxic effect in C6
glioma cells in both in vitro and in vivo conditions, and indicated that such treatment method using both
enzyme/
prodrug therapy and TRAIL
immunotherapy might be a promising therapeutic strategy in treating
glioma.