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 (∼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.
Yeh
Cheng-Chang
CC
Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan.
Hsieh
Hsiao-Ling
HL
Lee
Jihjong
J
Jan
Yi-Hua
YH
Lai
Tsung-Ching
TC
Hong
Chi-Yuan
CY
Hsiao
Michael
M
Kuo
Mark Y P
MY
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D053208:Kaplan-Meier Estimate; D051379:Mice; D016513:Mice, SCID; D009062:Mouth Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D009374:Neoplasms, Experimental; D011094:Polyethyleneimine / Q000494:pharmacology*; D011897:Random Allocation; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D015996:Survival Rate; D014162:Transfection / Q000379:methods; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000627:therapeutic use*
D051017:Apoptosis Regulatory Proteins; C488588:PUMA protein, mouse; D025521:Tumor Suppressor Proteins; D011094:Polyethyleneimine; D045304:Cytochromes c; D053148:Caspase 3