Cyclooxygenase-2 is up-regulated by interleukin-1β in human colorectal cancer cells via multiple signaling pathways

Wenbiao Liu, Niels Reinmuth, Oliver Stoeltzing, Alexander A. Parikh, Carmen Tellez, Simon Williams, Young D. Jung, Fan Fan, Akihiko Takeda, Morihisa Akagi, Menashe Bar-Eli, Gary E. Gailick, Lee M. Ellis

Research output: Contribution to journalArticlepeer-review


Overexpression of cyclooxygenase-2 (COX-2) has been observed in human colorectal cancer. COX-2 expression in human tumors can be induced by growth factors, cytokines, oncogenes, and other factors. The mechanisms regulating COX-2 expression in human colon cancer have not been completely elucidated. We hypothesized that the proinflammatory cytokine interleukin-1β (IL-1β) mediates COX-2 expression in HT-29 human colon cancer cells. Treatment of HT-29 cells with IL-1β induced expression of COX-2 mRNA and protein in a time- and dose-dependent manner. Inhibitors of the extracellular signal-regulated kinase 1/2, c-Jun NH2-terminal kinase, P38 mitogen-activated protein kinase, and nuclear factor-κB (NF-κB) signaling pathways blocked the ability of IL-1β to induce COX-2 mRNA. In contrast, Wortmannin, a phosphoinositide 3-kinase inhibitor upstream of protein kinase B/Akt, led to a slight increase in COX-2 mRNA expression after IL-1β treatment. Electrophoretic mobility shift assay on nuclear extracts demonstrated that IL-1β induced NF-κB DNA binding activity in HT-29 cells, and the activated NF-κB complex was eliminated after treatment with an inhibitor of NF-κB. Supershift assay indicated that the two NF-κB subunits, p65 and p5O, were involved in activation of NF-κB complex by IL-1β stimulation. The stability of COX-2 mRNA was not altered by IL-1β to treatment. These data demonstrate that IL-1β induces COX-2 expression in HT-29 cells through multiple signaling pathways and NF-κB.

Original languageEnglish (US)
Pages (from-to)3632-3636
Number of pages5
JournalCancer Research
Issue number13
StatePublished - Jul 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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