POLYETHYLENIMINE-MEDIATED PUMA GENE DELIVERY TO ORTHOTOPIC ORAL CANCER: SUPPRESSION OF TUMOR GROWTH THROUGH APOPTOSIS INDUCTION IN SITU AND PROLONGED SURVIVAL

Background. PUMA (a p53 up-regulated modulator of apoptosis) is induced by p53 tumor suppressor and other apoptotic stimuli. It was found to be a principal mediator of cell death in response to diverse apoptotic signals, implicating PUMA as a likely tumor suppressor. Methods. In this study, we examined the efficacy of targeted PUMA gene therapy in human oral cancer (SAS) cells using polyethylenimine (PEI)-mediated transfection for gene delivery. Results. Exogenous expression of PUMA in SAS cells resulted in apoptosis with cytochrome c release, activation of caspase-3 and -9, and cleavage of PARP. Gene delivery of PEI/PUMA in SAS xenografts induced apoptosis and resulted in significant reductions (similar to 60%) of tumor growth in vivo. Furthermore, we have shown that PEI-mediated PUMA gene therapy prolonged survival of animals with orthotopic SAS oral cancers. Conclusions. Taken together, these results indicated that PUMA gene therapy via PEI delivery could be a promising method for the treatment of oral squamous cell carcinoma. (C) 2010 Wiley Periodicals, Inc. Head Neck 33: 878-885, 2011