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Cited by 103Cancer, Hypoxia, and MetabolismGlioma Diagnosis and TreatmentRadiation Therapy and Dosimetry

HIF-1α inhibition by siRNA or chetomin in human malignant glioma cells: effects on hypoxic radioresistance and monitoring via CA9 expression

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Kessler, Jacqueline, Hahnel, Antje, Wichmann, Henri, Rot, Swetlana, Kappler, Matthias, Bache, Matthias, Vordermark, Dirk·2010·BMC Cancer
DOI 10.1186/1471-2407-10-605PMC PMC2992520
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Abstract

BACKGROUND: Hypoxia induces activation of the HIF-1 pathway and is an essential characteristic of malignant gliomas. Hypoxia has been linked to tumor progression, therapy resistance and poor prognosis. However, little is known about the impact of HIF-1α inhibition on radioresistance of malignant glioma. METHODS: In this study, we investigated the effects of the inhibition of HIF-1α on cell survival and radiosensitivity in U251MG and U343MG glioma cells, using two different strategies. HIF-1α inhibition was achieved by siRNA targeting of HIF-1α or via chetomin, a disruptor of interactions between HIF-1α and p300. The inhibition of the HIF-1 pathway was monitored by quantitative real-time PCR and Western blot analyses of the expression levels of HIF-1α and CA9. CA9 expression was investigated as a potential indicator of the efficacy of HIF-1 inhibition and the resulting radiosensitivity of malignant glioma cell lines was determined by clonogenic assay after irradiation under normoxic (2-10 Gy) or hypoxic (2-15 Gy) conditions. RESULTS: Although siRNA and chetomin show distinct modes of action, both attenuated the hypoxia-induced radioresistance of malignant glioma cell lines U251MG (DMF10: 1.35 and 1.18) and U343MG (DMF10: 1.78 and 1.48). However, siRNA and chetomin showed diverse effects on radiosensitivity under normoxic conditions in U251MG (DMF10: 0.86 and 1.35) and U343MG (DMF10: 1.33 and 1.02) cells. CONCLUSIONS: Results from this in vitro study suggest that inhibition of HIF-1α is a promising strategy to sensitize human malignant gliomas to radiotherapy and that CA9 could serve as an indicator of effective HIF-1-related radiosensitization.

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  • Disruption of HIF-p300 interactions by chetomin results in marked repression of HIF-dependent transcription in vitro and in murine xenograft models.

    “Disruption of HIF–p300 interactions by chetomin results in marked repression of HIF-dependent transcription in vitro and in murine xenograft models [[397], [398], [399]].”

    From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [399]

    The Background describes chetomin as disrupting HIF-1α–p300 interactions and attenuating hypoxia-inducible gene expression. The Results report substantial reductions in CA9 expression in cultured glioma cells, although one hypoxic-cell result was not statistically significant. The paper describes its study as in vitro; it does not report repression of HIF-dependent transcription in murine xenograft models. (LLM, conf=0.90)

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Cited by

Sorted by citations

Authors
Kessler, J., Hahnel, A., Wichmann, H., Rot, S., Kappler, M., Bache, M., & Vordermark, D.
Affiliations
Martin Luther University Halle-Wittenberg (DE)
Corresponding author
Kessler, Jacqueline
ORCID
Venue
BMC Cancer
Publisher
Springer Science and Business Media LLC
Published
2010-11-04
Volume
10
Issue
1
Pages
605-605
ISSN
1471-2407 (ISSN-L)
DOI
10.1186/1471-2407-10-605
PMC
PMC2992520
OpenAlex
W2071178476
Cited by
103
References
2
Citations by year
2026: 3 · 2025: 2 · 2024: 9 · 2023: 4 · 2022: 7 · 2021: 9 · 2020: 6 · 2019: 6 · 2018: 8 · 2017: 4 · 2016: 5 · 2015: 12 · 2014: 10 · 2013: 6 · 2012: 7
FWCI
1.71
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Cancer (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Deutsche Forschungsgemeinschaft
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Radiation Therapy and Dosimetry
Keywords
HIF-1α, high-grade glioma, radiosensitization, chetomin, P300, carbonic anhydrase IX, siRNA, HIF-1 signaling, clonogenic survival, U251 cells, radiotherapy
MeSH terms
Carbonic Anhydrase IX, Hypoxia, Antigens, Neoplasm, Antineoplastic Agents, Carbonic Anhydrases, Cell Survival, Disulfides, Glioma, Humans, Gene Expression Regulation, Neoplastic, Apoptosis, Disease Progression, Drug Resistance, Neoplasm, Reverse Transcriptase Polymerase Chain Reaction, Indole Alkaloids, RNA, Small Interfering, Cell Line, Tumor, Hypoxia-Inducible Factor 1, alpha Subunit

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