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

(Background & Aims) under bar: 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) under bar: A cell-proliferation assay was used to determine the response of HCA-7 cells to the HER-3/HER-4 ligand heregulin beta -1 (HRG beta -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) under bar: HCA-7 cells express HER-2/neu messenger RNA and protein, and exposure of these cells to HRG beta -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) under bar: 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.