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Polish Journal of Surgery

The Journal of Foundation of the Polish Journal of Surgery

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Celecoxib - A Selective Cyclooxygenase-2 Inhibitor Exhibits Dose - Dependent Chemopreventive Activity on an Animal Model of Colorectal Cancer*

Michał Spychalski1 / Łukasz Dziki1 / Jarosław Buczyński1 / Andrzej Kulig1 / Stanisław Sporny1 / Adam Dziki1

Department of General and Colorectal Surgery, Medical University, Łódź, Kierownik: prof. dr hab. A. Dziki1

Department of Clinical Pathology, Polish Mother's Memorial Hospital Research Institute, Kierownik: prof. dr hab. A. Kulig2

Department of Dentist's Pathology, Medical University, Łódź, Kierownik: dr hab. S. Sporny, prof. nadzw.3

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Citation Information: Polish Journal of Surgery. Volume 80, Issue 5, Pages 248–255, ISSN (Print) 0032-373X, DOI: 10.2478/v10035-008-0032-3, June 2008

Publication History

Published Online:
2008-06-09

Celecoxib - A Selective Cyclooxygenase-2 Inhibitor Exhibits Dose - Dependent Chemopreventive Activity on an Animal Model of Colorectal Cancer*

Colorectal cancer (CRC) is still one of the unresolved issues in medicine. Despite constant improvements in diagnosis and treatment, the prognosis for CRC is unsatisfactory. In recent years, much attention has been paid to experiments concerning chemoprevention of CRC.

The aim of the study was evaluation of the effectiveness of celecoxib, a selective Cyclooxygenase-2 (COX-2) inhibitor of chemically-induced CRC carcinogenesis in Fisher F344 rats.

Material and methods. Forty-five four-week old male F344 rats were randomized into four groups. In Groups 1, 2, and 3, we induced the CRC carcinogenesis through two subcutaneous injections of Azoxymethane in doses of 20 mg/kg. Rats from groups 1 and 2 were treated with celecoxib in doses of 10 and 30 mg/kg from the start of the experiment. Group 4 was a negative control. The experiment ended in the 26th week. We assessed the following parameters: the number of Aberrant Crypt Foci (premalignant lesions in colons) and the immunoexpression indexes: COX-2, Vascular Endothelial Growth Factor (VEGF), and c-myc.

Results. Celecoxib reduced the ACF number. The ACF reduction was dose-dependent. The median ACF number per field of vision was as follows for each of the groups: 1.7, 0.75, 3.2, and 0.2. Celecoxib, irrespective of the dose, reduced the VEGF immunoexpression index. We did not observe a reduction of COX-2 or c-myc immunoexpression in the celecoxib groups.

Conclusions. In this experiment, we proved that celecoxib possessed chemopreventive activity. Carcinogenesis inhibition by selective COX-2 inhibitor was dose-dependent. We demonstrated that celecoxib hidners angiogenesis, expressed as VEGF immunoexpression. We indirectly confirmed the hypothesis of a celecoxib COX-2 independent pathway mechanism of action.

Keywords: chemoprevention; COX-2; celecoxib; ACF; VEGF; c-myc; NF κB

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