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Journal of Korean Neurosurgical Society > Volume 25(8); 1996 > Article
Journal of Korean Neurosurgical Society 1996;25(8): 1561-1567.
Gene Therapy of Brain Tumors:Effects of Adenovirus-mediated Wild Type p53 Gene Transfer in Human Glioma Cells.
Yong Kil Hong, W K Alfred Yung
1Department of Neurosurgery, Catholic University Medical College, Seoul, Korea.
2Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
The p53 tumor suppressor gene is one of the genes with greatest therapeutic potential for cancer treatment and its growth inhibitory mechanism is thought to be mediated through the activation of its downstream mediator, WAF1/Clip1. In this study, we evaluated the effect of the replication-defective recombinant adenovirus expressing wild-type p53 gene(Ad5CMV-p53) in human glioma cell lines(U-251, LG) harboring mutant-type p53. beta-galactosidase histochemistry revealed that 90% of the U-251 and 42% the of LG cells are infected with the adenovirus at a multiplicity of infection(MOI) of 25 plaque-forming units(PFU)/cell. Immunoblot analyses showed that endogenous p53 protein is expressed at a high level, and significant exogenous p53 protein expression and WAF1/Clip 1 induction peaked on day 1 and day 3 after Ad5CMV-p53 treatment. Introduction of Ad5CMV-p53 inhibited the cell rowth of U-251(85% inhibition) and LG cells(36% inhibition), and influenced cell morphology. The optimal dose of Ad5CMV-p53 for the tumor cel ls growth inhibition was MOI of 10-40 PFU/cell. These results suggest that Ad5CMV-p53 infects human glioma cells and transduces the p53 gene with high efficiency, and could be further developed for the gene therapy of human gliomas.
Key Words: Gene therapy; P53; Adenovirus; Human glioma
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