Dexamethasone suppresses DU145 cell proliferation and cell cycle through inhibition of the extracellular signal-regulated kinase 1/2 pathway and cyclin D1 expression / 亚洲男科学杂志(英文版)
Asian Journal of Andrology
; (6): 635-641, 2008.
Article
em En
| WPRIM
| ID: wpr-359974
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>AIM</b>To determine the mechanisms of glucocorticoids in inhibiting advanced prostate cancer growth.</p><p><b>METHODS</b>The cell proliferation and cell cycle of prostate cancer DU145 cells following dexamethasone treatment were determined by proliferation assay and fluorescence-activated cell sorter. Western blot analysis was carried out to evaluate the effects of dexamethasone on phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and expression of cyclin D1 in DU145 cells with or without glucocorticoid receptor (GR) antagonist RU486. Reverse transcription-polymerase chain reaction verified the expression of GR mRNA in DU145 cells.</p><p><b>RESULTS</b>Dexamethasone significantly inhibited DU145 cell proliferation at the G(0)/G(1) phase. Western blot analysis showed a dramatic reduction of ERK1/2 activity and cyclin D1 expression in dexamethasone-treated cells. The decreased phosphorylation of ERK1/2 in dexamethasone-treated cells was attenuated by GR blockade. Additionally, the effects of dexamethasone in inhibiting cyclin D1 expression were altered by GR blockade.</p><p><b>CONCLUSION</b>Dexamethasone suppresses DU145 cell proliferation and cell cycle, and the underlying mechanisms are through the inhibition of phosphorylation of ERK1/2 and cyclin D1 expression. The inhibition of ERK1/2 phosphorylation and cyclin D1 expression is attenuated by GR blockade, suggesting that GR regulates ERK1/2 and cyclin D1 pathways. These observations suggest that dexamethasone has a potential clinical application in prostate cancer therapy.</p>
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Índice:
WPRIM
Assunto principal:
Patologia
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Farmacologia
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Neoplasias da Próstata
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RNA Mensageiro
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Dexametasona
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Transdução de Sinais
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Receptores de Glucocorticoides
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Regulação Neoplásica da Expressão Gênica
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Ciclo Celular
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Antineoplásicos Hormonais
Limite:
Humans
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Male
Idioma:
En
Revista:
Asian Journal of Andrology
Ano de publicação:
2008
Tipo de documento:
Article