Targeting cyclooxygenase 2 and HER-2/neu pathways inhibits colorectal carcinoma growth

Moss Mann, Hongmiao Sheng, Jinyi Shao, Christopher S. Williams, Paul I. Pisacane, Mark X. Sliwkowski, Raymond N. DuBois

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172 Scopus citations

Abstract

Background & Aims: The cyclooxygenase 2 (COX-2) and ErbB/HER pathways are important modulators of cancer cell growth. We sought to determine the effects of treatment with a specific COX-2 inhibitor and/or a monoclonal antibody against the ErbB receptor subtype HER-2/neu on carcinoma cell growth. Methods: A cell-proliferation assay was used to determine the response of HCA-7 cells to the HER-3/HER-4 ligand heregulin β-1 (HRGβ-1). Both in vitro and in vivo assays were used to determine the effects of the selective COX-2 inhibitor, celecoxib, and/or an anti-HER-2/neu monoclonal antibody (either Herceptin [Genetech Inc., S. San Francisco, CA] or 2C4) on cell growth. Results: HCA-7 cells express HER-2/neu messenger RNA and protein, and exposure of these cells to HRGβ-1 results in a significant stimulation of cell growth. Celecoxib or Herceptin inhibits HCA-7 cell growth in vitro and in vivo. Combination therapy with celecoxib plus Herceptin or celecoxib plus 2C4 resulted in additive effects that resulted in almost complete inhibition of tumor growth. Conclusions: Combined treatment with COX-2 and HER-2/neu inhibitors more effectively reduces colorectal carcinoma growth than either agent alone. Therefore, targeting of both the COX-2 and ErbB signaling pathways may represent a novel approach for the treatment and/or prevention of colorectal cancer in humans.

Original languageEnglish (US)
Pages (from-to)1713-1719
Number of pages7
JournalGastroenterology
Volume120
Issue number7
DOIs
StatePublished - Jan 1 2001

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Mann, M., Sheng, H., Shao, J., Williams, C. S., Pisacane, P. I., Sliwkowski, M. X., & DuBois, R. N. (2001). Targeting cyclooxygenase 2 and HER-2/neu pathways inhibits colorectal carcinoma growth. Gastroenterology, 120(7), 1713-1719. https://doi.org/10.1053/gast.2001.24844