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Polyethylenimine‐mediated PUMA gene delivery to orthotopic oral cancer: Suppression of tumor growth through apoptosis induction in situ and prolonged survival
Author(s) -
Yeh ChengChang,
Hsieh HsiaoLing,
Lee Jihjong,
Jan YiHua,
Lai TsungChing,
Hong ChiYuan,
Hsiao Michael,
Kuo Mark Y. P.
Publication year - 2011
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/hed.21555
Subject(s) - puma , apoptosis , genetic enhancement , gene delivery , cancer research , polyethylenimine , transfection , cancer , biology , programmed cell death , cytochrome c , medicine , gene , genetics
Abstract 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 (∼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. © 2010 Wiley Periodicals, Inc. Head Neck, 2011