We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
292. Polyethylenimine Mediated Oral Cancer Targeted PUMA Gene Delivery Suppressed Tumor Growth and Prolonged Survival.
- Authors
Benson Chen; Ming-Shyan Huang; Steven Yeh; Kuo, Mark Y. P.; Hsiao, Michael
- Abstract
PUMA, a BH3-only protein, induced by the 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. In this study, we examined the efficacy of polyethylenimine (PEI)-mediated targeted PUMA gene therapy in preclinical in-situ oral cancers. The highest trasnfection efficiency (40 %) without cytotoxicity was achieved with PEI/DNA weight ratio of 0.75 in SAS cells. Exogenous expression of PUMA in SAS cells resulted in apoptosis as evidenced by cytochrome c release from mitochondria to cytoplasm, activating caspases-9, caspase-3 and PARP. Direct injections of PEI complexed EGFP reporter gene plasmids into SAS tumor established in SCID mouse resulted in high transfection efficiency without obvious cytotoxicity. Gene delivery of tumor targeted PUMA expression vector with survivin promoter into SAS xenografts resulted in significant reductions (70 %, p<0.0001) of tumor growth in vivo. Induction of apoptosis was observed in PEI/PUMA treated tumors by TUNEL staining analysis. Furthermore, PEI mediated systemic survivin promoter-PUMA gene delivery resulted in prolonged survival of animal with orthotopic DsRed2-SAS oral cancers. Taken together, these results indicated targeted PUMA gene therapy via PEI delivery could be a promising method for the treatment of oral SCC Fig 1.Molecular Therapy (2006) 13, S111–S111; doi: 10.1016/j.ymthe.2006.08.347
- Subjects
PROTEINS; TUMORS; CELL death; CYTOCHROME c; CELL-mediated cytotoxicity
- Publication
Molecular Therapy, 2006, Vol 13, pS111
- ISSN
1525-0016
- Publication type
Article
- DOI
10.1016/j.ymthe.2006.08.347