Abstract
The anti-tumor effect of a selective cyclooxygenase (COX)-2 inhibitor, JTE-522, was examined with the human head and neck squamous cell carcinoma cell line KB. KB cells do not produce prostaglandin (PG)-E2. In vitro, JTE-522 induced an increase of G1 phase-arrested cells, suppression of platelet-derived growth factor (PDGF) production and inhibition of telomerase activity. No cytotoxic effect was detected. In vivo, the growth of the tumor xenografted into nude mice was significantly suppressed by JTE-522. Suppression of angiogenesis at the periphery of the tumor, increase of G1-arrested cells and suppression of telomerase activity were observed, together with an increase of apoptotic cell death in the tumor. Immunological enhancement did not play a role. We concluded that the anti-tumor effect of JTE-522 was caused by anti-angiogenesis action, cell cycle arrest and inhibition of telomerase activity of the tumor cells. These combined effects might induce apoptosis.
MeSH terms
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Animals
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Benzenesulfonates / pharmacology*
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Carcinoma, Squamous Cell / drug therapy
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Carcinoma, Squamous Cell / immunology
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Carcinoma, Squamous Cell / pathology*
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Cell Cycle / drug effects*
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Cell Division / drug effects
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Cyclooxygenase 2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors / pharmacology*
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Cytotoxicity, Immunologic
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Female
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G1 Phase
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Head and Neck Neoplasms / drug therapy
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Head and Neck Neoplasms / immunology
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Head and Neck Neoplasms / pathology*
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Humans
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Isoenzymes / metabolism*
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KB Cells
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Killer Cells, Lymphokine-Activated / immunology
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Killer Cells, Natural / immunology
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Membrane Proteins
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Mice
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Mice, Nude
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Oxazoles / pharmacology*
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Platelet-Derived Growth Factor / genetics
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Prostaglandin-Endoperoxide Synthases / metabolism*
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Telomerase / metabolism
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Transplantation, Heterologous
Substances
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4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide
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Benzenesulfonates
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors
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Isoenzymes
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Membrane Proteins
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Oxazoles
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Platelet-Derived Growth Factor
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Cyclooxygenase 2
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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Telomerase