Reduced tumour progression and angiogenesis in 1,2-dimethylhydrazine mice treated with NS-398 is associated with down-regulation of cyclooxygenase-2 and decreased beta-catenin nuclear localisation
| Autor: | Massimo Pignatelli, Jennifer Baker, Richard S. Daly, Moganaden Moorghen, Andrea Buda, Nahida A. Banu |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Adenoma
medicine.medical_specialty Angiogenesis Clinical Biochemistry Apoptosis chemistry.chemical_compound Mice Cyclin D1 Internal medicine medicine Animals Cyclooxygenase Inhibitors Nitrobenzenes beta Catenin Cell Proliferation Cell Nucleus Mice Inbred BALB C Sulfonamides Factor VIII biology Neovascularization Pathologic Cell growth Cell Biology General Medicine Neoplasms Experimental medicine.disease 1 2-Dimethylhydrazine Tumor Burden Endocrinology chemistry Bromodeoxyuridine Cyclooxygenase 2 Colonic Neoplasms biology.protein Carcinogens Prostaglandins Female Cyclooxygenase TCF Transcription Factors Signal Transduction |
| Zdroj: | Cell communicationadhesion. 18(1-2) |
| ISSN: | 1543-5180 |
| Popis: | Cyclooxygenase (COX)-2 is a key molecular target of colon cancer prevention. However, the mechanisms by which COX-2 inhibitors confer protective effects against tumour development are not completely understood. The aim of this study was to elucidate the effects of NS-398 in the 1,2-dimethylhydrazine (DMH) mouse model with respect to alteration in the expression of COX-2 and E-cadherin-catenin complex. Alterations in cell proliferation, apoptosis, and vascular density were investigated. NS-398 showed reduced COX-2 immunoreactivity in adenomas with a decrease in vascular density in non-dysplastic mucosa. Adenomas revealed increased E-cadherin and beta-catenin reactivity. NS-398 reduced the percentages of tumour cells with nuclear localisation of beta-catenin and cyclin D1. Bromodeoxyuridine (BrdUrd) index in adenomas was significantly higher in untreated animals. NS-398 resulted in significant increase in apoptosis in adenomas. Our results suggest a protective role of NS-398 on tumour development associated with reduced COX-2 expression, reduced vascular density and perturbation of beta-catenin signalling pathway. |
| Databáze: | OpenAIRE |
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