Enhancement of Hypoxia-Induced Tumor Cell Death In vitro and Radiation Therapy In vivo by Use of Small Interfering RNA Targeted to Hypoxia-Inducible Factor-1α
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Hypoxia-inducible factor-1α (HIF-1α) is an important transcriptional factor that is activated when mammalian cells experience hypoxia, a tumor microenvironmental condition that plays pivotal roles in tumor progression and treatment. In this study, we examined the idea of down-regulating HIF-1α in tumor cells for therapeutic gain. We show that the expression levels of HIF-1α can be significantly attenuated by use of the recently established small interfering RNA technology in combination with adenovirus-mediated gene transfer. Down-regulation of the HIF-1α protein enhanced hypoxia-mediated tumor cell apoptosis in vitro. Subcutaneous tumor growth was also prevented from cells with attenuated HIF-1α expression. In addition, intratumoral injection of adenovirus encoding the HIF-1α-targeted small interfering RNA had a small but significant effect on tumor growth when combined with ionizing radiation. Therefore, our results provide proof of HIF-1α as an effective target for anticancer therapy. They also suggest that an adenovirus-based small interfering RNA gene transfer approach may be a potentially effective adjuvant strategy for cancer treatment.
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Silencing or pharmacological inhibition of HIF-1α can increase the anti-tumor effects of IR.
“Importantly, silencing or pharmacological inhibition of HIF-1α can increase the anti-tumor effects of IR (Zhang et al., 2004;Moeller et al., 2005;Harada et al., 2009;Harada et al., 2012).”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Zhang et al., 2004
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- Authors
- Zhang, X., Kon, T., Wang, H., Li, F., Huang, Q., Rabbani, Z. N., Kirkpatrick, J. P., Vujaskovic, Z., Dewhirst, M. W., & Li, C.-Y.
- Affiliations
- Duke Medical Center (US)
- 1Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina; and
- Shanghai Jiao Tong University (CN)
- ORCID
- Venue
- Cancer Research
- Published
- 2004-11-15
- Volume
- 64
- Issue
- 22
- Pages
- 8139-8142
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2126372787
- Cited by
- 120
- References
- 20
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 2 · 2020: 2 · 2018: 3 · 2017: 3 · 2016: 6 · 2015: 5 · 2014: 4 · 2013: 7 · 2012: 11
- FWCI
- 4.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA82512)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- hypoxia-inducible factor-1α, HIF-1α, siRNA, adenoviral gene transfer, tumor hypoxia, tumor cell apoptosis, radiotherapy, ionizing radiation, subcutaneous tumor growth, intratumoral injection, cancer gene therapy, tumor microenvironment
- MeSH terms
- Base Sequence, Cell Line, Humans, Radiotherapy, Transcription Factors, Cell Hypoxia, Polymerase Chain Reaction, Apoptosis, DNA Primers, RNA, Small Interfering, Cell Line, Tumor, Hypoxia-Inducible Factor 1, alpha Subunit
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