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Published on: February 22, 2015
Targeted-simultaneous expression of Gas1 and p53 using a bicistronic adenoviral vector in gliomas
J A Benítez1, L Arregui, P Vergara
1Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, México DF, México.
Abstract:
The targeted expression of transgenes is one of the principal goals of gene therapy, and it is particularly relevant for the treatment of brain tumors. In this study, we examined the effect of the overexpression of human gas1 (growth arrest specific 1) and human p53 cDNAs, both under the transcriptional control of a promoter of the human glial fibrillary acidic protein (gfa2), employing adenoviral expression vectors, in glioma cells. We showed that the targeted overexpression of gas1 and p53 (AdSGas1 and AdSp53, respectively) in rat glioma cells (C6) reduced the number of viable cells and induced apoptosis. Moreover, the adenovirally targeted expression of these genes also reduced tumor growth in vivo. Unexpectedly, there was no additive effect when both gas1 and p53 were simultaneously expressed in the same cells using a bicistronic adenoviral vector. We suggest that Gas1 does not act in combination with p53 in the C6 and U373 glioma cell lines, inducing apoptosis and cell cycle arrest. Our results indicate that the targeted expression of tumor suppressor genes (gas1 and p53) regulated by the gfa2 promoter, together with adenoviral vectors may provide an interesting approach for adjuvant selective glioma gene therapy.
Insights
Targeted gene therapy using adenoviral vectors to overexpress growth arrest specific 1 (Gas1) and p53 suppressed glioma cell growth and tumor progression. Simultaneous expression did not enhance these effects.
Area of Science:
- Oncology
- Gene Therapy
- Molecular Biology
Background:
- Targeted transgene expression is crucial for gene therapy, especially for brain tumors like gliomas.
- Adenoviral vectors offer a method for targeted gene delivery.
- Growth arrest specific 1 (Gas1) and p53 are tumor suppressor genes with potential therapeutic applications.
Purpose of the Study:
- To investigate the effects of overexpressing human Gas1 and p53 using adenoviral vectors under the glial fibrillary acidic protein (gfa2) promoter in glioma cells.
- To evaluate the therapeutic potential of Gas1 and p53 in reducing glioma cell viability and tumor growth.
- To determine if simultaneous expression of Gas1 and p53 has an additive effect on glioma cells.
Main Methods:
- Utilized adenoviral expression vectors to deliver human Gas1 and p53 cDNAs.
- Employed the human glial fibrillary acidic protein (gfa2) promoter for targeted gene expression in glioma cells.
- Assessed cell viability, apoptosis, and tumor growth in vitro and in vivo.
Main Results:
- Targeted overexpression of Gas1 (AdSGas1) and p53 (AdSp53) in rat C6 glioma cells reduced viable cell numbers and induced apoptosis.
- Adenovirally mediated expression of Gas1 and p53 significantly inhibited tumor growth in vivo.
- No additive therapeutic effect was observed when Gas1 and p53 were co-expressed using a bicistronic adenoviral vector.
Conclusions:
- Targeted overexpression of Gas1 and p53, regulated by the gfa2 promoter via adenoviral vectors, demonstrates potential for selective glioma gene therapy.
- Gas1 and p53 appear to act independently rather than synergistically in inducing apoptosis and cell cycle arrest in the C6 and U373 glioma cell lines.
- This approach offers a promising strategy for adjuvant therapy in glioma treatment.
