Eradication of p53-mutated head and neck squamous cell carcinoma xenografts using nonviral p53 gene therapy and photochemical internalization

Mol Ther. 2006 Jun;13(6):1156-62. doi: 10.1016/j.ymthe.2006.02.003. Epub 2006 Mar 27.


Photochemical internalization (PCI) technology has been used for PEI-mediated p53 gene transfer in mice bearing head and neck squamous cell carcinoma (HNSCC) xenografts. Using luciferase as a reporter gene, PCI led to a 20-fold increase in transgene expression 48 h after transfection and sustained transgene expression for 7 days. Therefore, iterative p53 gene transfer was performed by means of a weekly single injection of PEIGlu4/p53 complexes alone or with PCI for 5 (group A) or 7 (group B) weeks. The efficiency of p53 gene therapy was evaluated by following tumor growth and expression of P53-related downstream proteins (P21, MDM2, Bcl2, Bax). Apoptosis induction was evidenced through caspase-3 activation and PARP cleavage. Using PCI, tumor growth inhibition was observed in all transfected animals. Further, successful tumor cure was achieved in 17% (group A) and 83% (group B) of animals. PCI-mediated p53 gene transfer led to higher P53 protein expression that was correlated with induction of Bax and P21 proapoptotic proteins, repression of Bcl2 as well as activation of caspase-3, and cleavage of PARP. The present study demonstrates that PCI enhances the in vivo efficiency of PEI-mediated p53 gene transfer and can be proposed for p53 gene therapy in HNSCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / therapy*
  • Caspase 3
  • Caspases / metabolism
  • Combined Modality Therapy
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Female
  • Gene Expression
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Luciferases / genetics
  • Mice
  • Mutation*
  • Photochemotherapy / methods*
  • Photosensitizing Agents / pharmacology
  • Poly(ADP-ribose) Polymerases / metabolism
  • Polyethyleneimine / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-mdm2 / genetics
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism
  • Xenograft Model Antitumor Assays
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism


  • Cyclin-Dependent Kinase Inhibitor p21
  • Photosensitizing Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Polyethyleneimine
  • Luciferases
  • Proto-Oncogene Proteins c-mdm2
  • Poly(ADP-ribose) Polymerases
  • CASP3 protein, human
  • Casp3 protein, mouse
  • Caspase 3
  • Caspases