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.
Ivanov
Marie-Agnès
MA
GENCELL SA, 72-82 rue Léon Geffroy, 94400 Vitry-sur-Seine, France.
Lamrihi
Badia
B
GENCELL SA, 72-82 rue Léon Geffroy, 94400 Vitry-sur-Seine, France.
Szyf
Moshe
M
Department of Pharmacology and Therapeutics, McGill University, 3655 Drummond Street, Montreal, PQ H3G 1Y6, Canada.
Scherman
Daniel
D
Unité de Pharmacologie Chimique et Génétique FRE CNRS 2463, Université René Descartes, Faculté de Pharmacie, 4 avenue de l'observatoire, 75270 Paris cedex 06, France.
Bigey
Pascal
P
Unité de Pharmacologie Chimique et Génétique FRE CNRS 2463, Université René Descartes, Faculté de Pharmacie, 4 avenue de l'observatoire, 75270 Paris cedex 06, France.
D000818:Animals; D001761:Bleomycin / Q000494:pharmacology / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D016373:DNA, Antisense; D004268:DNA-Binding Proteins / Q000235:genetics*; D018274:Electroporation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007273:Injections, Intramuscular; D051379:Mice; D009374:Neoplasms, Experimental / Q000628:therapy*; D010957:Plasmids; D014407:Tumor Cells, Cultured
D016373:DNA, Antisense; D004268:DNA-Binding Proteins; C115368:MBD2 protein; D001761:Bleomycin