Electroporation-mediated transfer of cytokine genes into human esophageal tumors produces anti-tumor effects in mice.
Electroporation facilitates transfer of chemicals or plasmid DNA from extracellular milieu into cells by increasing the permeability of the cell membrane. Delivery of electric pulses to established tumors thereby can improve the susceptibility of tumors to an anti-cancer agent administered. We examined whether electroporation-mediated transfer of cytokine genes into solid tumors could produce anti-tumor effects in the tumor-bearing mice. Plasmid DNA containing cytokine genes were injected into human esophageal T.Tn tumors developed in nude mice and electric pulses were then delivered. Administration of murine GM-CSF or human IL-2 gene followed by electroporation significantly suppressed the subsequent growth of T.Tn tumors and prolonged the survival of the inoculated mice. In contrast, electroporation-mediated introduction of a control gene, human GM-CSF gene, whose products do not bind to murine GM-CSF receptors, did not achieve any anti-tumor effects. In vivo transfection of cytokine genes with electroporation could be a possible therapeutic strategy for established solid tumors.
Matsubara
H
H
Department of Surgery (II), Chiba University School of Medicine, Japan. matsuhm@srgy201.m.chiba-u.ac.jp
Gunji
Y
Y
Maeda
T
T
Tasaki
K
K
Koide
Y
Y
Asano
T
T
Ochiai
T
T
Sakiyama
S
S
Tagawa
M
M
D000818:Animals; D018274:Electroporation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000628:therapy*; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D007376:Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor