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


CONCLUSIONS
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.
Gao
Qing-Zhen
QZ
Friendship Nephrology Center and Blood Purification Center, Jinan City Central Hospital, Shandong University School of Medicine, Jinan, China.
Lu
Jia-Ju
JJ
Liu
Zi-Dong
ZD
Zhang
Hui
H
Wang
Shao-Mei
SM
Xu
He
H
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000187:drug effects / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D018931:Antineoplastic Agents, Hormonal; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D019938:Cyclin D1; D003907:Dexamethasone; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3