Enhanced antitumor activity of a combination of MBD2-antisense electrotransfer gene therapy and bleomycin electrochemotherapy

J Gene Med. 2003 Oct;5(10):893-899. doi: 10.1002/jgm.438.

Abstract

Background: MBD2 is a methylated DNA-binding protein that has been previously suggested to have transcriptional silencing as well as DNA demethylase activities. We have previously shown that electrotransfer of an MBD2-antisense encoding plasmid inhibits tumor growth in vivo. In this study we tested whether a combination of MBD2-antisense gene therapy and bleomycin chemotherapy has an augmented antitumor effect in comparison with either monotherapy.

Methods: Mice bearing human non-small-cell lung carcinoma line H1299 xenoplants were treated with electrotransfer of either bleomycin or MBD2-antisense expression plasmid or a combination of both therapies and tumor growth following treatment was monitored.

Results: A combination of electrotransfer of MBD2-antisense and bleomycin electrochemotherapy has an additive inhibitory effect on the rate of tumor growth and a synergistic effect on the number of tumor-free animals when compared with either monotherapy.

Conclusions: Our results suggest that a combination of MBD2-antisense electrotransfer gene therapy and chemotherapy with bleomycin is a candidate new approach to anticancer therapy.

Publication types

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

MeSH terms

  • Animals
  • Bleomycin / pharmacology
  • Bleomycin / therapeutic use*
  • Combined Modality Therapy
  • DNA, Antisense
  • DNA-Binding Proteins / genetics*
  • Electroporation
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Humans
  • Injections, Intramuscular
  • Mice
  • Neoplasms, Experimental / therapy*
  • Plasmids
  • Tumor Cells, Cultured

Substances

  • DNA, Antisense
  • DNA-Binding Proteins
  • MBD2 protein
  • Bleomycin