title: Celecoxib exerts antitumor effects in canine mammary tumor cells via COX‑2‑independent mechanisms.
abstract: Celecoxib plays antitumor roles via multiple mechanisms in a variety of human cancers. The aim of this study was to clarify the mechanism of action of celecoxib in canine mammary tumors. We examined the antitumor effects of celecoxib in AZACB canine mammary tumor cells expressing low levels of cyclooxygenase‑2 (COX‑2) to minimize the effect of COX‑2 on its activity. Our data revealed that celecoxib inhibited cell proliferation mainly via COX‑2‑independent mechanisms. Specifically, celecoxib decreased the proportion of cells in S phase and increased G2/M arrest, which was associated with increased expression of the cyclin‑dependent kinase inhibitors (CDKIs) p21 and p27. In addition, treatment with celecoxib downregulated COX‑2 expression, and induced apoptosis via both the intrinsic and extrinsic pathways. These findings suggest that celecoxib might be a useful agent for the treatment of canine mammary tumors, regardless of COX‑2 expression. In the future, it might be possible to use a combination of celecoxib and other antitumor agents to treat canine mammary tumors.
authors.affiliation: Laboratory of Veterinary Pharmacology, Nihon University College of Bioresource Sciences, Fujisawa, Kanagawa 252‑8510, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Tamura
authors.affiliation: Laboratory of Veterinary Pharmacology, Nihon University College of Bioresource Sciences, Fujisawa, Kanagawa 252‑8510, Japan.
authors.forename: Teruyoshi
authors.initials: T
authors.lastname: Saito
authors.affiliation: Laboratory of Veterinary Pharmacology, Nihon University College of Bioresource Sciences, Fujisawa, Kanagawa 252‑8510, Japan.
authors.forename: Kanae
authors.initials: K
authors.lastname: Murata
authors.affiliation: Laboratory of Veterinary Pharmacology, Nihon University College of Bioresource Sciences, Fujisawa, Kanagawa 252‑8510, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kawashima
authors.affiliation: Laboratory of Veterinary Pharmacology, Nihon University College of Bioresource Sciences, Fujisawa, Kanagawa 252‑8510, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Asano
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000068579:Celecoxib; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004283:Dog Diseases / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004285:Dogs; D005260:Female; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D016196:S Phase / Q000187:drug effects / Q000235:genetics; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D018844:Cyclin-Dependent Kinases; D000068579:Celecoxib