Potential of adenoviral p53 gene therapy and irradiation for the treatment of malignant gliomas
| Autor: | Youn Ju Yang, Chul Seung Kay, Sei Chul Yoon, Yong Kil Hong, Young Ae Joe, Ihl Bhong Choi, In Ah Kim, Chang Min Kim, Hee Chung Kwon, Joon-Ki Kang |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Cancer Research
Cell Survival Cell Genetic Vectors Apoptosis Biology Adenoviridae Glioma medicine Tumor Cells Cultured Humans Cytotoxicity Clonogenic assay Cell Nucleus Brain Neoplasms Genetic transfer Cell Cycle Dose-Response Relationship Radiation Transfection Genetic Therapy Cell cycle medicine.disease Flow Cytometry Genes p53 Combined Modality Therapy medicine.anatomical_structure Oncology Cell culture Mutation Cancer research |
| Zdroj: | International journal of oncology. 19(5) |
| ISSN: | 1019-6439 |
| Popis: | We investigated the combined effects of p53 gene transfer and irradiation and its still unclear interaction mechanism in human gliomas. Four human glioma cell lines expressing mutant type p53 (U373 and A172) and wild-type p53 (D54MG and EFC-2) were transfected by adenoviral vectors bearing p53 gene at 50 multiplicity of infection. Two days after transfection, cells were irradiated (3, 6, and 9 Gy). The cytotoxicity was evaluated by clonogenic assay. The quantitative analysis of apoptosis and cell cycle analysis were performed using flow cytometry. Irradiation combined with adenoviral p53 transfection significantly increased cytotoxicity, which was additive in cell lines with wild-type p53 and more than additive in cell lines with mutant p53. The combination of two modalities increased the apoptotic population by 14% in A172 cells and 20% in D54 MG cells, which were the sum of apoptosis from each modality. Adenoviral p53 transfection increased the G1 phase fraction and concomitant decrease of radioresistant S phase fraction in A172 and D54MG cells. Our study demonstrated that p53 gene transfer combined with irradiation increased absolute cytotoxicity in human glioma cells used in this experiment. The interaction mechanism for increased cytotoxicity involved, in part, increased apoptosis and change of cell cycle profile. |
| Databáze: | OpenAIRE |
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