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.
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Authors | Y Shimazu, K Kurozumi, T Ichikawa, K Fujii, M Onishi, J Ishida, T Oka, M Watanabe, Y Nasu, H Kumon, I Date |
Journal | Gene therapy
(Gene Ther)
Vol. 22
Issue 2
Pg. 146-54
(Feb 2015)
ISSN: 1476-5462 [Electronic] England |
PMID | 25394252
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adaptor Proteins, Signal Transducing
- Antineoplastic Agents
- Chemokines
- DKK3 protein, human
- Integrins
- Intercellular Signaling Peptides and Proteins
- Peptides, Cyclic
- Snake Venoms
- Cilengitide
- CASP8 protein, human
- CASP9 protein, human
- Caspase 8
- Caspase 9
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Topics |
- Adaptor Proteins, Signal Transducing
- Adenoviridae
(genetics)
- Animals
- Antineoplastic Agents
(pharmacology, therapeutic use)
- Apoptosis
- Astrocytes
(metabolism)
- Brain Neoplasms
(therapy)
- Caspase 8
(metabolism)
- Caspase 9
(metabolism)
- Cell Line, Tumor
- Chemokines
- Combined Modality Therapy
- Female
- Gene Knockdown Techniques
- Genetic Therapy
- Glioma
(therapy)
- Humans
- Integrins
(antagonists & inhibitors)
- Intercellular Signaling Peptides and Proteins
(genetics, metabolism)
- Mice, Inbred BALB C
- Mice, Nude
- Peptides, Cyclic
(pharmacology)
- Snake Venoms
- Transduction, Genetic
- Xenograft Model Antitumor Assays
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