Anti-EGFR and ErbB-2 antibodies attenuate cyclooxygenase-2 expression and cooperatively inhibit survival of human colon cancer cells.
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.
Half
Elizabeth
E
Department of Gastrointestinal Medicine & Nutrition, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Sun
Yunjie
Y
Sinicrope
Frank A
FA
D000906:Antibodies / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors; D066246:ErbB Receptors / Q000276:immunology / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D009578:Nitrobenzenes / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology
D000906:Antibodies; D051546:Cyclooxygenase 2; D016861:Cyclooxygenase Inhibitors; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D009578:Nitrobenzenes; D018719:Erb-b2 Receptor Tyrosine Kinases; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C512478:EGFR protein, human; C508053:ERBB2 protein, human