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In vivo antitumor efficacy of STAT3 blockade using a transcription factor decoy approach: implications for cancer therapy
- Source :
- Oncogene. 24:970-979
- Publication Year :
- 2004
- Publisher :
- Springer Science and Business Media LLC, 2004.
-
Abstract
- The development of more effective prevention and treatment strategies for solid tumors is limited by an incomplete understanding of the critical growth pathways that are activated in carcinogenesis. Signal transducers and activators of transcription (STAT) proteins have been linked to transformation and tumor progression. Several approaches have been used to block STAT3 in cancer cells resulting in reduced proliferation and apoptosis. We tested the hypothesis that blocking STAT3 activation using a transcription factor decoy approach would decrease tumor growth and STAT3 target gene expression in vivo. In a xenograft model of squamous cell carcinoma of the head and neck (SCCHN), daily administration of the STAT3 decoy (25 microg) resulted in decreased tumor volumes, abrogation of STAT3 activation, and decreased expression of STAT3 target genes (VEGF, Bcl-xL, and cyclin D1) compared to treatment with a mutant control decoy. Blockade of STAT3 with the STAT3 decoy also induced apoptosis and decreased proliferation, an effect that was augmented when the STAT3 decoy was combined with cisplatin, both in vitro and in vivo. These results suggest that a transcription factor decoy approach may be used to target STAT3 in cancers that demonstrate increased STAT3 activation including SCCHN.
- Subjects :
- STAT3 Transcription Factor
Vascular Endothelial Growth Factor A
Cancer Research
Transplantation, Heterologous
bcl-X Protein
Down-Regulation
Mice, Nude
Antineoplastic Agents
Apoptosis
Biology
medicine.disease_cause
Mice
Growth factor receptor
Genetics
medicine
Animals
Humans
Cyclin D1
Epidermal growth factor receptor
STAT3
Molecular Biology
Transcription factor
Cell Proliferation
Genetic Therapy
DNA-Binding Proteins
Cell Transformation, Neoplastic
Proto-Oncogene Proteins c-bcl-2
Head and Neck Neoplasms
Tumor progression
Cancer cell
Carcinoma, Squamous Cell
Trans-Activators
Cancer research
biology.protein
Cisplatin
Carcinogenesis
Decoy
Acute-Phase Proteins
Signal Transduction
Transcription Factors
Subjects
Details
- ISSN :
- 14765594 and 09509232
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....d696c4fc315da14eb86976a0f9306bb7