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

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. Copyright (C) 2003 John Wiley Sons, Ltd.