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Integrin antagonist augments the therapeutic effect of adenovirus-mediated REIC/Dkk-3 gene therapy for malignant glioma
- Source :
- Gene Therapy. 22:146-154
- Publication Year :
- 2014
- Publisher :
- Springer Science and Business Media LLC, 2014.
-
Abstract
- Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) was identified as a gene whose expression is reduced in many human cancers. REIC/Dkk-3 expression is also downregulated in malignant glioma and regulates cell growth through caspase-dependent apoptosis. cRGD (EMD121974), an antagonist of integrins, has demonstrated preclinical efficacy against malignant glioma. In this study, we investigated the antiglioma effect of combination therapy using an adenovirus vector carrying REIC/Dkk-3 (Ad-REIC) and cRGD. Quantitative real-time reverse-transcription PCR revealed the reduction of REIC/Dkk-3 mRNA levels in malignant glioma cell lines. The reduction of REIC/Dkk-3 protein expression in malignant glioma cell lines was also confirmed with western blot analysis. After treatment with Ad-REIC and cRGD, the proliferative rate of malignant glioma cells was significantly reduced in a time-dependent manner. In vivo, there was a statistically significant increase in the survival of mice treated with Ad-REIC and cRGD combination therapy compared with Ad-REIC monotherapy. We identified an apoptotic effect following monotherapy with Ad-REIC. Moreover, cRGD augmented the antiglioma efficacy of Ad-REIC. These results may lead to a promising new approach for the treatment of malignant glioma.
- Subjects :
- Integrins
Combination therapy
Genetic enhancement
Mice, Nude
Antineoplastic Agents
Apoptosis
Biology
Peptides, Cyclic
Adenoviridae
Viral vector
Transduction, Genetic
In vivo
Cell Line, Tumor
Glioma
Genetics
medicine
Animals
Humans
Molecular Biology
Adaptor Proteins, Signal Transducing
Caspase 8
Mice, Inbred BALB C
Brain Neoplasms
Cell growth
Genetic Therapy
medicine.disease
Combined Modality Therapy
Xenograft Model Antitumor Assays
Caspase 9
Astrocytes
Gene Knockdown Techniques
Cancer research
Intercellular Signaling Peptides and Proteins
Molecular Medicine
Female
Chemokines
Immortalised cell line
Snake Venoms
Subjects
Details
- ISSN :
- 14765462 and 09697128
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Gene Therapy
- Accession number :
- edsair.doi.dedup.....1361da7182af6f4db858ccf7b20e4f32