High antitumor activity using intratumoral injection of plasmid DNA with mutant-type p27Kip1 gene following in vivo electroporation.
In this study, we attempted to use a non-viral gene transfer system, in vivo electroporation, in oral cancer cell B88 xenografts. To evaluate this in vivo gene transfer method, the GFP gene was transfected into xenografts by electroporation. Then, the efficiency of transfection of exogenous p27Kip1 gene by electroporation was confirmed by Western blot analysis. Next, to estimate the reduction of oral cancer xenografts by this method, we measured the size of B88 xenografts in nude mice after electroporation with the wild- or mutant-type p27Kip1 gene. The growth of tumors was markedly suppressed by mutant-type p27Kip1 gene transfection by electroporation compared with transfection of wild-type p27Kip1 gene or empty vector only. Moreover, histological specimens revealed apoptotic cell death was increased in mutant-type p27Kip1-transfected tumors compared to wild-type or empty vector only. These results suggest that it is possible to transfer mutant-type p27Kip1 into oral cancer xenografts using electroporation and to suppress the growth of tumors, furthermore, it is suggested that this system might be used for oral cancer.
Harada
Koji
K
Second Department of Oral and Maxillofacial Surgery, University of Tokushima, School of Dentistry, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan. harako@dent.tokushima-u.ac.jp
Supriatno
Kawaguchi
Shin-Ichi
S
Onoue
Tomitaro
T
Kawashima
Yuichiro
Y
Yoshida
Hideo
H
Sato
Mitsunobu
M
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018274:Electroporation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007267:Injections; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000628:therapy*; D009368:Neoplasm Transplantation; D018307:Neoplasms, Squamous Cell / Q000628:therapy*; D010957:Plasmids; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27