Radio-responsive gene therapy for malignant glioma cells without the radiosensitive promoter: Caspase-3 gene therapy combined with radiation.
Caspase-3 plays a critical role as an executioner of apoptosis. The aim of this study is to evaluate the potential of the combination of caspase-3 gene therapy and radiation treatment. We prepared a plasmid (pCI-CSP3) that contained the human caspase-3 gene and the cytomegalovirus promoter. We introduced this plasmid into U251 and U87 human glioma cells and subjected the cells to radiation treatment. The degree of cell death and apoptosis were evaluated. None of the cell lines underwent apoptosis by the overexpression of caspase-3 alone, but the degree of cell death and apoptosis were markedly enhanced by the addition of radiation treatment. Next, we prepared another plasmid (EGR-CSP3) that contained the caspase-3 gene and a radiation-sensitive promoter. Each treatment system using either pCI-CSP3 or EGR-CSP3 showed radio response. The treatment system using pCI-CSP3 more effectively induced apoptosis than that using EGR-CSP3. Caspase-3 gene therapy in combination with radiation treatment has the potential to serve as a radio-responsive gene therapy without any radiation-sensitive promoter.
Tsurushima
Hideo
H
Department of Biomedical Engineering, Medical School, Johns Hopkins University, Baltimore, MD, USA. hideo-tsurushima@aist.go.jp
Yuan
Xuan
X
Dillehay
Larry E
LE
Leong
Kam W
KW
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects*; D053148:Caspase 3 / Q000235:genetics* / Q000378:metabolism; D061945:Caspase Inhibitors; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D003131:Combined Modality Therapy; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003587:Cytomegalovirus / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D051766:Early Growth Response Protein 1 / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods; D005910:Glioma / Q000235:genetics / Q000473:pathology / Q000628:therapy; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000528:radiation effects*; D011878:Radiotherapy / Q000379:methods; D014162:Transfection
D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D051766:Early Growth Response Protein 1; D009842:Oligopeptides; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; D053148:Caspase 3