Molecular mechanisms involved in the antiproliferative effect of two COX-2 inhibitors, nimesulide and NS-398, on colorectal cancer cell lines.
Dig Liver Dis
; 35(8): 557-65, 2003 Aug.
Article
em En
| MEDLINE
| ID: mdl-14567460
ABSTRACT
BACKGROUND:
Cyclooxygenase (COX)-2 is up-regulated in most colorectal cancers. Chronic use of non-steroidal anti-inflammatory drugs, which target cyclooxygenases, have been shown to reduce the risk of these cancers. However, the mechanisms underlying this protective effect remain unclear.AIMS:
The aim of our study was to characterize the effects of two COX-2 selective inhibitors, NS-398 and nimesulide, on colorectal cancer cell proliferation, and to describe the molecular mechanisms involved. MATERIALS ANDMETHODS:
HT-29 and SW-1116 cell lines were cultured with either NS-398 or nimesulide. Cell proliferation was assessed by staining DNA with crystal violet. Cell cycle repartition and apoptosis were analysed by flow cytometry. The expression of COX-1 and COX-2. and of two cyclin dependent kinase inhibitors, p21Cip1 and p27Kip1, was analysed by Western blotting and RT-PCR.RESULTS:
Both drugs dose-dependently inhibited cell proliferation and induced G1 cell cycle blockade. HT-29 cells were more sensitive to both drugs than SW-1116 cells. p21Cip1 and p27Kip1 were induced on both cell lines. Concomitant induction of p21Cip1 mRNA indicates transcriptional modulation, whereas induction of p27Kip1 only at the protein level suggests post-translational modulation.CONCLUSION:
NS-398 and nimesulide inhibit colorectal cell proliferation through induction of p21Cip1 and p27Kip1.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Problema de saúde:
6_colon_rectum_cancers
Assunto principal:
Sulfonamidas
/
Neoplasias Colorretais
/
Adenocarcinoma
/
Divisão Celular
/
Inibidores de Ciclo-Oxigenase
/
Nitrobenzenos
Limite:
Humans
Idioma:
En
Revista:
Dig Liver Dis
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
França