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

Nahida A. Banu, Richard S. Daly, Andrea Buda, Moganaden Moorghen, Jennifer Baker, Massimo Pignatelli

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalCell Communication and Adhesion
Volume18
Issue number1-2
DOIs
Publication statusPublished - Feb 2011
Externally publishedYes

Fingerprint

1,2-Dimethylhydrazine
beta Catenin
Cyclooxygenase 2
Tumors
Down-Regulation
Adenoma
Blood Vessels
Cadherins
Neoplasms
Apoptosis
Catenins
Cyclooxygenase 2 Inhibitors
Cyclin D1
Cell proliferation
Bromodeoxyuridine
Colonic Neoplasms
Mucous Membrane
Animals
Cells
Cell Proliferation

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry

Cite this

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. / Banu, Nahida A.; Daly, Richard S.; Buda, Andrea; Moorghen, Moganaden; Baker, Jennifer; Pignatelli, Massimo.

In: Cell Communication and Adhesion, Vol. 18, No. 1-2, 02.2011, p. 1-8.

Research output: Contribution to journalArticle

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