地塞米松快速抑制卵巢癌细胞系ERK1/2活性

背景与目的:细胞外信号调节的激酶1/2(extracellularsignal-regulatedkinase1/2,ERK1/2)的激活在多种细胞增殖的过程中发挥重要作用。作者曾经发现人工合成的糖皮质激素地塞米松(dexamethasone,Dex)可显著抑制人卵巢癌细胞系HO-8910的增殖。本研究试图观察Dex对HO-8910细胞ERK1/2活性的影响,以探讨其抑制该细胞增殖的信号转导通路。方法:以Westernblot方法测定ERK1/2在HO-8910细胞中的活性,细胞计数方法检测细胞增殖的改变。结果:1×10-7mol/LDex作用于HO-8910细胞5min即出现ERK1和ERK2活性的同步降低,最大作用出现在30min,与对照相比,二者分别减少41%和54%(P均<0.001),4h恢复至对照水平。ERK1/2活性降低的程度随Dex浓度(1×10-10～1×10-6mol/L)升高而增大。该作用不能被糖皮质激素受体(glucocorticoidreceptor,GR)拮抗剂RU486所阻断。ERK1/2上游激酶MEK1/2的抑制剂PD98059也具有抑制该细胞增殖作用,并能增强Dex对细胞增殖的抑制。结论:Dex能够以不依赖GR的方式快速抑制HO-8910细胞ERK1/2活性,这可能与其抑制细胞增殖过程有关。

Rapid inhibition of extracellular signal-regulated kinase 1/2 in a human ovarian cancer cell line by dexamethasone

BACKGROUND & 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. CONCLUSION: 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.