[Rapid inhibition of extracellular signal-regulated kinase 1/2 in a human ovarian cancer cell line by dexamethasone].
OBJECTIVE
Activation of extracellular signal-regulated kinase 1/2 (ERK1/2) plays an important role in cell proliferation of a variety of cell types. The authors had previously found that dexamethasone (Dex), a synthetical glucocorticoid, can markedly inhibit the proliferation of a human ovarian cancer cell line HO-8910. This study was designed to observe the effect of Dex on the activation of ERK1/2 in HO-8910 cells in order to explore the signal transduction pathway that mediates the anti-proliferation effect of Dex on these cells.


METHODS
The activation of ERK1/2 was determined by Western blot analysis, and changes of cell proliferation were examined by cell count.


RESULTS
Inhibition of activation of ERK1 and ERK2 by 1 x 10(-7) mol/L Dex occurred synchronously at 5 min, with maximum up to 41% and 54%, respectively at 30 min compared with the control (P < 0.001), and sustained until 4 h. The effect increased with the increasement of concentration of Dex (1 x 10(-10)-1 x 10(-6) mol/L). RU486, an antagonist of glucocorticoid receptor (GR), did not block the effect. PD98059, an inhibitor of MEK1/2, also inhibited HO-8910 cell proliferation and could enhance the growth-inhibition effect of Dex.


CONCLUSIONS
Dex can rapidly inhibit ERK1/2 activation in a GR-independent manner in HO-8910 cells, which might play a role in Dex-mediated growth inhibition.
Xia
Bing
B
Department of Pathophysiology, Second Military Medical University, Shanghai 200433, P. R. China. xia-bing@21cn.com
Lu
Jian
J
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects* / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000473:pathology; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
D018931:Antineoplastic Agents, Hormonal; D004791:Enzyme Inhibitors; D005419:Flavonoids; D015735:Mifepristone; D003907:Dexamethasone; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one