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 © 2003 John Wiley & Sons, Ltd.