Dexamethasone suppresses DU145 cell proliferation and cell cycle through inhibition of the extracellular signal-regulated kinase 1/2 pathway and cyclin D1 expression.

Published

Journal Article

AIM: To determine the mechanisms of glucocorticoids in inhibiting advanced prostate cancer growth. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Full Text

Duke Authors

Cited Authors

  • Gao, Q-Z; Lu, J-J; Liu, Z-D; Zhang, H; Wang, S-M; Xu, H

Published Date

  • July 2008

Published In

Volume / Issue

  • 10 / 4

Start / End Page

  • 635 - 641

PubMed ID

  • 18097517

Pubmed Central ID

  • 18097517

Electronic International Standard Serial Number (EISSN)

  • 1745-7262

International Standard Serial Number (ISSN)

  • 1008-682X

Digital Object Identifier (DOI)

  • 10.1111/j.1745-7262.2008.00352.x

Language

  • eng