摘要
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。
Background &Objective:Activation of extracellular signal-regulated kinase 1/2(ERK1/2)plays an important role in cell proliferatio n of a variety of cell types.The authors had previously found that dexamethasone(Dex),a synthetical glucocorticoid,can ma rkedly 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 ERK1/2in HO-8910cells in order to explore the sig nal transduction pathway that mediates the anti-proliferation effect of De x on these cells.Methods:The activation of ERK1/2was determined by Western blot analy sis,and changes of cell proliferati on were examined by cell count.Results:Inhibition of activation of ERK1and ERK2by 1×10 -7 mol /L Dex occurred synchronously at5min,with maximum up to 41%and54%,respectively at 30min compared with the control(P<0.001),and sustained until 4h.The effect i ncreased with the increasement of concentration o f Dex(1×10 -10 -1×10 -6 mol /L).RU486,an antagonist of glucocorti coid receptor(GR),did not block the effect.PD98059,a n inhibitor of MEK1/2,also inhibite d HO-8910cell proliferation and cou ld enhance the growth-inhibition effe ct of Dex.Conclusion:Dex can rapidly inhibit ERK1/2activ ation in a GR-independent manner in HO-8910cells,which might play a role in Dex-mediated growth in hibition.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2002年第8期868-871,共4页
Chinese Journal of Cancer
关键词
地塞米松
人卵巢癌细胞系
细胞外信号调节的激酶
细胞增殖
Dexamethasone
Human ovarian cancer cell line
Extracellular signal-regulated kinase
Cell proliferatio n