Combinatory anti-tumor effects of electroporation-mediated chemotherapy and wild-type p53 gene transfer to human esophageal cancer cells

Delivery of electric pulses to an established solid tumor augments the perm eability of cell membrane and increases the susceptibility of tumors to an anti-cancer agent that is administered in the vicinity of tumors. Forced ex pression of the wild-type p53 gene in tumor cells that have non-functional p53 gene(s) can also enhance their sensitivity to a DNA-damaging agent. To investigate the feasibility of electroporation-mediated therapy for cancer, electric pulses were delivered to human esophageal tumors developed in nud e mice after they received an anti-cancer agent and/or plasmid DNA containi ng the wild-type p53 gene. The growth of esophageal tumors was suppressed w ith electroporation-mediated chemotherapy compared with the treatment with an anti-cancer agent or electroporation alone. Intratumoral injection of th e wild-type p53 gene into p53-mutated esophageal tumors followed by electro poration also inhibited tumor growth. When mice were administered with the wild-type p53 gene and an anti-cancer agent, subsequent electroporation pro duced a synergistic therapeutic effect. Combinatory transfer of plasmid DNA and a pharmacological agent by electroporation is thereby a possible thera peutic strategy fur the treatment of solid tumors.