The effects of L-748706, a selective cyclooxygenase-2 inhibitor, on N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis
| Autor: | Haiyan Qin, Miranda E. Rose, Robeena M. Aziz, Rakesh Dixit, Peter S. Carlton, Gary D. Stoner, Tong Chen |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
Cancer Research Pathology medicine.medical_specialty Esophageal Neoplasms medicine.medical_treatment Pharmacology medicine.disease_cause Piroxicam Dinoprostone Gene Expression Regulation Enzymologic Dimethylnitrosamine 4-Butyrolactone medicine Animals Cyclooxygenase Inhibitors RNA Messenger Sulfones Esophagus biology Cyclooxygenase 2 Inhibitors Cell growth business.industry Anti-Inflammatory Agents Non-Steroidal Cancer General Medicine medicine.disease Rats Inbred F344 Rats medicine.anatomical_structure Tumor progression Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases biology.protein Carcinogens Carcinoma Squamous Cell Cyclooxygenase Carcinogenesis business Prostaglandin E medicine.drug |
| Zdroj: | Carcinogenesis. 26(9) |
| ISSN: | 0143-3334 |
| Popis: | Epidemiological studies suggest that the frequent intake of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a decreased risk of developing esophageal squamous cell carcinoma (SCC). This decrease is thought to correlate with the inhibition of cyclooxygenase (COX) activity. The production of prostaglandin E 2 (PGE 2 ), a major metabolite of COX, is increased in numerous human cancers including esophageal SCC, therefore, inhibition of COX activity and subsequent suppression of the formation of PGE 2 may be chemopreventive in the esophagus. The objective of the present study was to determine whether L-748706 (L-706), a novel selective COX-2 inhibitor, would prevent N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumor progression in the Fischer 344 (F344) rat. In rats pretreated with a low-dose of NMBA (0.25 mg/kg body weight), L-706 at 100 p.p.m. in the diet significantly reduced tumor multiplicity but not tumor incidence. At 150 p.p.m. in the diet, L-706 alone and in combination with 200 p.p.m. piroxicam produced significant reductions in both tumor incidence and multiplicity. Inhibition of tumor development in low-dose NMBA-treated rats was associated with reductions in esophageal cell proliferation rates and PGE 2 levels in preneoplastic tissues. In contrast, in rats treated with a higher dose of NMBA (0.5 mg/kg body weight), neither L-706 alone nor in combination with piroxicam reduced esophageal tumor incidence or multiplicity in spite of the fact that they reduced esophageal PGE 2 levels in preneoplastic tissues and in papillomas. Cell proliferation rates were reduced only in animals treated with L-706 + piroxicam. Our data suggest that the chemopreventive treatments were effective in inhibiting tumor development in NMBA-treated animals only when they reduced PGE 2 levels in preneoplastic esophageal tissues approximately to those levels found in normal esophagus. |
| Databáze: | OpenAIRE |
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