Anti-EGFR and ErbB-2 antibodies attenuate cyclooxygenase-2 expression and cooperatively inhibit survival of human colon cancer cells

Elizabeth Half, Yunjie Sun, Frank A Sinicrope

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Cyclooxygenase-2 (COX-2) is a transcriptional target and downstream effector of the ErbB-1 (EGFR) and ErbB-2 signaling pathways. We found that anti-EGFR and anti-ErbB-2 antibodies inhibited ERK phosphorylation and downregulated COX-2 protein expression in HCA-7 human colon carcinoma cells. Both antibodies also augmented the cytotoxic effects of the selective COX-2 inhibitor, NS-398. Inhibition of EGFR and ErbB-2 attenuated cell growth by increasing cell death, and the antibody combination suppressed cell growth to a greater extent than did either antibody alone. In conclusion, EGFR and ErbB-2 regulate ERK-mediated COX-2 expression and their selective inhibition enhanced NS-398-induced cell death. Cooperative inhibition of cell growth by EGFR and ErbB-2 blockade suggests the therapeutic potential of targeting multiple ErbB receptors.

Original languageEnglish (US)
Pages (from-to)237-246
Number of pages10
JournalCancer Letters
Volume251
Issue number2
DOIs
StatePublished - Jun 28 2007

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Keywords

  • Cetuximab
  • COX-2
  • EGFR
  • ErbB-2
  • NS-398
  • Trastuzumab

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

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