title: Combined cetuximab and celecoxib treatment exhibits a synergistic anticancer effect on human oral squamous cell carcinoma in vitro and in vivo.
abstract: The aim of the present study was to evaluate the potency of epidermal growth factor receptor (EGFR) pathway inhibition achieved by combining cetuximab (CET), an anti-EGFR monoclonal antibody, and celecoxib (CXB), a cyclooxygenase-2 (COX-2) inhibitor, in oral squamous cell carcinoma (OSCC) in vitro and in vivo. The OSCC cell line, HSC3, was treated with CET (0-400 μg/ml), CXB (0-40 μM), or a combination of both at a range of concentrations. Cell proliferation, apoptosis, migration and invasion were determined to assess the anticancer effects in vitro. The in vivo effects of CET and CXB on tumor cell growth were examined using an OSCC xenograft nude mouse model. In addition, downstream protein expression levels of EGFR, p-EGFR, PI3K, p-PI3K, AKT and p-Akt were evaluated by western blot analysis. It was found that the combination of low concentrations of CET and CXB significantly suppressed the proliferation, migration and invasion of the HSC3 tumor cells and decreased PEG2 production and VEGF expression in vitro, and inhibited tumor growth in vivo compared to the action of either agent alone. The results also showed that this combination significantly induced apoptosis and increased caspase-3 and caspase-8 activity compared to the action of either agent alone (P<0.01). Furthermore, the combination treatment significantly reduced the expression of p-EGFR, p-PI3K and p-Akt in the HSC3 cell line, which may contribute to the inhibition of tumor growth. Taken together, our findings revealed that the additive combination of CET and CXB is a potential drug candidate for the treatment of OSCC.
authors.forename: Ming
authors.initials: M
authors.lastname: Qian
authors.forename: Donghua
authors.initials: D
authors.lastname: Qian
authors.forename: Hongyu
authors.initials: H
authors.lastname: Jing
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Chengyuan
authors.initials: C
authors.lastname: Ma
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D000068579:Celecoxib; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D000068818:Cetuximab; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism; D006258:Head and Neck Neoplasms; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D000077195:Squamous Cell Carcinoma of Head and Neck; D013449:Sulfonamides / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; D019869:Phosphatidylinositol 3-Kinases; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D000068579:Celecoxib; D015232:Dinoprostone; D000068818:Cetuximab