Polyethylenimine-mediated PUMA gene delivery to orthotopic oral cancer: suppression of tumor growth through apoptosis induction in situ and prolonged survival

Head Neck. 2011 Jun;33(6):878-85. doi: 10.1002/hed.21555. Epub 2010 Aug 24.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Apoptosis / genetics*
  • Apoptosis / physiology
  • Apoptosis Regulatory Proteins / therapeutic use*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / therapy*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cytochromes c / genetics
  • Cytochromes c / metabolism
  • Disease Models, Animal
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Humans
  • In Situ Nick-End Labeling
  • In Vitro Techniques
  • Kaplan-Meier Estimate
  • Mice
  • Mice, SCID
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / mortality
  • Mouth Neoplasms / pathology
  • Mouth Neoplasms / therapy*
  • Neoplasms, Experimental
  • Polyethyleneimine / pharmacology*
  • Random Allocation
  • Sensitivity and Specificity
  • Statistics, Nonparametric
  • Survival Rate
  • Transfection / methods
  • Transplantation, Heterologous
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins / therapeutic use*

Substances

  • Apoptosis Regulatory Proteins
  • PUMA protein, mouse
  • Tumor Suppressor Proteins
  • Polyethyleneimine
  • Cytochromes c
  • Caspase 3