Cancer gene therapy using a pro-apoptotic gene, caspase-3.
Caspase-3 is a member of the cysteine protease family, which plays a crucial role in apoptosis. We applied the human caspase-3 gene as a novel form of anticancer gene therapy. Overexpression of human caspase-3 alone could not induce apoptosis of tumor cell lines, but apoptosis was markedly enhanced by the addition of etoposide. In an AH130 liver tumor model, transduction of human caspase- 3, but not the empty vector, induced extensive apoptosis and reduced tumor volume when combined with etoposide administration. However, this effect was not observed with a Bcl-2 overexpressing tumor. In conclusion, caspase-3 gene transduction accompanied by an additional death stimulus may be a useful method of anticancer gene therapy, except for Bcl-2 overexpressing tumors.
Yamabe
K
K
The First Department of Surgery, Biomedical Research Center, Osaka University Medical School, Suita, Japan.
Shimizu
S
S
Ito
T
T
Yoshioka
Y
Y
Nomura
M
M
Narita
M
M
Saito
I
I
Kanegae
Y
Y
Matsuda
H
H
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D053148:Caspase 3; D020169:Caspases / Q000235:genetics*; D003131:Combined Modality Therapy; D005047:Etoposide / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D020287:In Situ Nick-End Labeling; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000628:therapy*; D009368:Neoplasm Transplantation; D019384:Nucleic Acid Synthesis Inhibitors / Q000627:therapeutic use; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects
D019384:Nucleic Acid Synthesis Inhibitors; D005047:Etoposide; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases