title: Piroxicam inhibits Masitinib-induced cyclooxygenase 2 expression in oral squamous cell carcinoma cells in vitro.
abstract: Development and characterization of animal models for human cancers is important for the improvement of diagnosis and therapy. The oral squamous cell carcinoma (OSCC) of domestic animals resembles human OSCC in many aspects; thus, cell lines derived from OSCC of cats and dogs are a valuable model for human OSCC. We characterized 1 feline OSCC (FeOSCC-Sidney) and 1 canine OSCC (K9OSCC-Abby) cell line and compared their characteristics with human OSCC cell line hSCC-25. We calculated the doubling time of the new OSCC cell lines and evaluated the expression profiles of cancer-related markers and cell-cycle proteins such as c-kit, platelet-derived growth factor receptor, vascular endothelial growth factor receptor, epidermal growth factor receptor, cyclooxygenase (COX)-1, COX-2, and p27 by immunocytochemistry and Western blot analysis. We evaluated the effects of novel receptor tyrosine kinase inhibitor (Masitinib, AB1010) and the nonsteroidal anti-inflammatory drug piroxicam on the previously mentioned OSCC cells. Interestingly, AB1010 increased expression levels of COX-2 in all tested OSCCs. Cotreatment of piroxicam with Masitinib significantly inhibited cell proliferation of OSCC as compared to either drug alone through the c-kit and AKT signaling pathways. Piroxicam inhibited Masitinib-induced COX-2 expression in all tested OSCCs. Therefore, targeting these two signaling pathways simultaneously was more efficient for inhibition of OSCCs across these species.
authors.affiliation: Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee.
authors.forename: Kusum
authors.initials: K
authors.lastname: Rathore
authors.affiliation: Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee.
authors.forename: Mary
authors.initials: M
authors.lastname: Alexander
authors.affiliation: Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee. Electronic address: mcekanov@utk.edu.
authors.forename: Maria
authors.initials: M
authors.lastname: Cekanova
mesh_terms: D000818:Animals; D001549:Benzamides; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism*; D002415:Cats; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004285:Dogs; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D010880:Piperidines; D010894:Piroxicam / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D001549:Benzamides; D016861:Cyclooxygenase Inhibitors; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D013844:Thiazoles; D010894:Piroxicam; D051546:Cyclooxygenase 2; C526575:masitinib