Nimesulide inhibits the growth of human esophageal carcinoma cells by inactivating the JAK2/STAT3 pathway.
Pathol Res Pract
; 211(6): 426-34, 2015 Jun.
Article
em En
| MEDLINE
| ID: mdl-25724470
ABSTRACT
Although selective COX-2 inhibitors have cancer-preventive effects and induce apoptosis, the mechanisms underlying these effects are not fully understood. This study investigated the effects of nimesulide, a selective COX-2 inhibitor, on apoptosis and on the JAK/STAT signaling pathway in Eca-109 human esophageal squamous carcinoma cells. The effects and mechanisms of nimesulide on Eca-109 cell growth were studied in culture and in nude mice with Eca-109 xenografts. Cells were cultured with or without nimesulide and/or the JAK2 inhibitor AG490. Cell proliferation was evaluated using the MTT assay, and apoptosis was investigated. COX-2 mRNA expression was measured using reverse transcription polymerase chain reaction, and protein expression was detected by Western blot analysis, immunohistochemistry, and flow cytometry. Nimesulide significantly inhibited Eca-109 cell viability in vitro in a dose- and time-dependent manner (P<0.05). Nimesulide also induced apoptosis, which was accompanied by a significant decrease in the expression of COX-2 and survivin and an increase in caspase-3 expression. Nimesulide downregulated the phosphorylation levels of JAK2 and STAT3, and JAK2 inhibition by AG490 significantly augmented both nimesulide-induced apoptosis and the downregulation of COX-2 and survivin (P<0.05). In vivo, nimesulide inhibited the growth of Eca-109 tumors and the expression of p-JAK2 and p-STAT3. Thus, nimesulide downregulates COX-2 and survivin expression and upregulates caspase-3 expression in Eca-109 cells, by inactivating the JAK2/STAT3 pathway. These effects may mediate nimesulide-induced apoptosis and growth inhibition in Eca-109 cells in vitro and in vivo.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sulfonamidas
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Neoplasias Esofágicas
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Carcinoma de Células Escamosas
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Ciclo-Oxigenase 2
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Fator de Transcrição STAT3
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Janus Quinase 2
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Pathol Res Pract
Ano de publicação:
2015
Tipo de documento:
Article