Cited by 121Cancer, Hypoxia, and MetabolismAngiogenesis and VEGF in CancerVirus-based gene therapy research

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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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Zhang, Xiuwu, Kon, Takashi, Wang, He, Li, Fang, Huang, Qian, Rabbani, Zahid N., Kirkpatrick, John P., Vujaskovic, Zeljko, Dewhirst, Mark W., Li, Chuan-Yuan·2004·Cancer Research

DOI 10.1158/0008-5472.can-03-2301

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Abstract

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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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: Zhang, Xiuwu
Li, Fang
Huang, Qian
Rabbani, Zahid N.
Kirkpatrick, John P.
Dewhirst, Mark W.
Li, Chuan-Yuan
Venue: Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2004-11-15
Volume: 64
Issue: 22
Pages: 8139-8142
ISSN: 0008-5472 (ISSN-L)
1538-7445
DOI: 10.1158/0008-5472.can-03-2301
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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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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