Targeted inhibition of Stat3 with a decoy oligonucleotide abrogates head and neck cancer cell growth

Leong, Paul L.; Andrews, Genevieve A.; Johnson, Daniel E.; Dyer, Kevin F.; Xi, Sichuan; Mai, Jeffrey C.; Robbins, Paul D.; Gadiparthi, Seshu; Burke, Nancy A.; Watkins, Simon F.; Grandis, Jennifer Rubin

doi:10.1073/pnas.0534764100

Cited by 341Cytokine Signaling Pathways and InteractionsHead and Neck Cancer StudiesNF-κB Signaling Pathways

Targeted inhibition of Stat3 with a decoy oligonucleotide abrogates head and neck cancer cell growth

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Leong, Paul L., Andrews, Genevieve A., Johnson, Daniel E., Dyer, Kevin F., Xi, Sichuan, Mai, Jeffrey C., Robbins, Paul D., Gadiparthi, Seshu +3 more·2003·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0534764100PMC PMC153061

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Abstract

The transcription factor signal transducer and activator of transcription 3 (Stat3) is constitutively activated in a variety of cancers including squamous cell carcinoma of the head and neck (SCCHN). Previous investigations have demonstrated that activated Stat3 contributes to a loss of growth control and transformation. To investigate the therapeutic potential of blocking Stat3 in cancer cells, we developed a transcription factor decoy to selectively abrogate activated Stat3. The Stat3 decoy was composed of a 15-mer double-stranded oligonucleotide, which corresponded closely to the Stat3 response element within the c-fos promoter. The Stat3 decoy bound specifically to activated Stat3 and blocked binding of Stat3 to a radiolabeled Stat3 binding element. By contrast, a mutated version of the decoy that differed by only a single base pair did not bind the activated Stat3 protein. Treatment of head and neck cancer cells with the Stat3 decoy inhibited proliferation and Stat3-mediated gene expression, but did not decrease the proliferation of normal oral keratinocytes. Thus, disruption of activated Stat3 by using a transcription factor decoy approach may serve as a novel therapeutic strategy for cancers characterized by constitutive Stat3 activation.

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Nucleic acid-based drugs, including decoy oligonucleotides and, perhaps, G-quartet oligonucleotides, inhibit STAT3-mediated gene expression and inhibit growth of different cancer cell lines.
“Nucleic acid–based drugs, including decoy oligonucleotides and, perhaps, G-quartet oligonucleotides, have been identified that inhibit STAT3-mediated gene expression and inhibit growth of different cancer cell lines (Leong et al., 2003; Lewis et al., 2008; Sun et al., 2008; Shen et al., 2009; Zhang et al., 2013b; Liu et al., 2014; Sen et al., 2014).”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Leong et al., 2003

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INVESTIGATION OF THE MECHANISM AND THERAPEUTIC POTENTIAL OF A TRANSCRIPTION FACTOR DECOY TARGETING SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION-3 (STAT3) FOR SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK (SCCHN)
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Abstract 4139: Development of a transcription factor decoy for efficient systemic administration in head and neck cancer
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Self-citation

Authors: Leong, P. L., Andrews, G. A., Johnson, D. E., Dyer, K. F., Xi, S., Mai, J. C., Robbins, P. D., Gadiparthi, S., Burke, N. A., Watkins, S. F., & Grandis, J. R.
Affiliations: University of Pittsburgh (US)
Departments of Otolaryngology, Medicine, Pharmacology, Molecular Genetics and Biochemistry, and Cell Biology and Physiology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15260
ORCID: Johnson, Daniel E.
Robbins, Paul D.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2003-03-14
Volume: 100
Issue: 7
Pages: 4138-4143
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0534764100
PMC: PMC153061
OpenAlex: W2143812692
Cited by: 340
References: 47
Citations by year: 2026: 5 · 2025: 4 · 2024: 13 · 2023: 11 · 2022: 6 · 2021: 8 · 2020: 13 · 2019: 14 · 2018: 10 · 2017: 3 · 2016: 8 · 2015: 20 · 2014: 16 · 2013: 23 · 2012: 25
FWCI: 7.21
Type: journal article
Language: en
Open access: green
europepmc.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Howard Hughes Medical Institute
American Academy of Otolaryngology-Head and Neck Surgery
National Institutes of Health
National Cancer Institute (CA77308, R01CA077308)
Topics: Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords: STAT3, transcription factor decoy, head and neck squamous cell carcinoma, c-fos promoter, constitutive STAT3 activation, tumor cell proliferation, oral keratinocytes
MeSH terms: Carcinoma, Squamous Cell, Cell Division, DNA-Binding Proteins, Head and Neck Neoplasms, Humans, Luciferases, Tumor Cells, Cultured, Trans-Activators, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Oligodeoxyribonucleotides, Antisense, STAT3 Transcription Factor, bcl-X Protein

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Targeted inhibition of Stat3 with a decoy oligonucleotide abrogates head and neck cancer cell growth

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