Inflammation, but not hypoxia, mediated HIF-1α activation depends on COX-2

Ioannis Stasinopoulos, David R. O'Brien, Zaver M. Bhujwalla

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


The COX pathway has been a target for pharmaceutical intervention in diseases with a high inflammatory component ranging from asthma and Alzheimer's to arthritis and cancer. A major transcriptional promoter of the malignant phenotype, HIF-1α, has been observed to be regulated by the COX-2 product PGE2. Here we show that HIF-1α protein significantly accumulated in human breast cancer MDA-MB-231 cells in response to the pro-inflammatory cytokine IL-1β, but not in COX-2-silenced MDA-MB-231 cells. In contrast HIF-1α expression could be detected in COX-2-silenced cells in response to the hypoxia-mimetic agent CoCl2 and hypoxia. Gene expression profiling in COX-2-containing and COX-2-silenced cells showed that the hypoxia-induced transcriptional response is largely unaffected by COX-2 silencing. These data suggest that the profound effects of COX-2 silencing on inhibiting invasion, tumor growth and metastasis from MDA-MB-231 cells are dependent on the induction of IL-1β-dependent COX-2 and HIF-1α but are independent of hypoxia.

Original languageEnglish (US)
Pages (from-to)31-35
Number of pages5
JournalCancer Biology and Therapy
Issue number1
StatePublished - Jan 2009


  • Breast cancer
  • COX-2
  • COX-2-silencing
  • HIF-1α
  • Hypoxia
  • Inflammation

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research


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