- Tsurushima, H. and Yuan, X. and Dillehay, L. E. and Leong, K. W., Radio-responsive gene therapy for malignant glioma cells without the radiosensitive promoter: Caspase-3 gene therapy combined with radiation,
Cancer Letters, vol. 246 no. 1-2
pp. 318-323 .
(last updated on 2010/06/11)
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. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
caspase-3 gene therapy radio-responsive gene therapy radiation radiation-sensitive promoter wild-type p53 adenovirus-mediated transfer thymidine kinase gene in-vivo ionizing-radiation transgene expression egr-1 promoter death activation ganciclovir