期刊文献+

糖皮质激素对人卵巢癌细胞系3AO细胞细胞外信号调节酶1和2活性的影响

Rapid effects of glucocorticoids on activity of extracellular signal-regulated kinase 1/2 in human ovarian cancer cell line 3AO
下载PDF
导出
摘要 目的观察糖皮质激素对人卵巢癌细胞系3AO细胞中丝裂原激活的蛋白激酶家族成员细胞外信号调节酶(ERK)1和2活性,以及ERK1/2抑制剂PD98089对3AO细胞增殖的影响。方法采用Western印迹法检测地塞米松(Dex)作用前后及未经药物处理(对照)组的ERK1和2蛋白活性,细胞增殖通过细胞计数完成。结果Dex(1×10^(-7)mol/L)处理3AO细胞5 min即出现ERK1和ERK2磷酸化程度降低,且两者呈同步变化;随着时间延长,ERK1和ERK2磷酸化程度明显降低,4 h时分别为处理前的25%和15%,具有时间依赖性;同时具有浓度抑制性,其中最大抑制出现在浓度为1×10^(-6)mol/L时,抑制率为85%;糖皮质激素受体(GR)拮抗剂RU486不能逆转这些效应。应用ERK1/2抑制剂PD98059处理3AO细胞,能够显著抑制细胞增殖,抑制程度与Dex组相同;而PD98059与Dex合用时可以增强两者单独应用时的抑制效应。结论Dex能够以不依赖GR的方式,快速抑制ERK蛋白活性,ERK信号通路可能参与抑制细胞增殖的过程。 Objective To study the effects of gluc0corticoids on the activity of extracellular signalregulated kinase (ERK) 1/2 in human ovarian cancer cell line 3AO and the inhibitory effect of PD98059, a ERK1/2 inhibitor, on the proliferation of 3AO cells. Methods Western blotting analysis was used to examine the activity of ERK1/2 before and after Dexamethasone (Dex) treatment. The cell proliferation was evaluated using viable cell count. Results Five minute treatment with 1×10^-7 mol/L Dex obviously decreased the phosphorylation of ERK1 and ERK2. The phosphorylation of ERK1 and ERK2 was obviously decreased; four hours after Dex treatment, their phosphorylation was 25 % and 15 % of the control, respectively. Furthermore, Dex decreased ERK1/2 in a time- and dose-ependent manner, with the maximum inhibition rate being 85 % when the concentration of Dex was 1 × 10^-6 mol/L. RU486, an antagonist of glucocorticoid receptor(GR), did not affect the above effects. PD98089, an antagonist of ERK1/2 upstream activating kinase MEK1/2, decreased the cell proliferation just like Dex; the combination of PD98059 and Dex had more potent inhibitory effect than the 2 were used alone. Conclusion Dex can rapidly inhibit ERK1/2 in a GR-independent manner in 3AO cells; the ERK pathway might participate in Dex-mediated cell inhibition.
作者 徐明娟 惠宁
出处 《上海医学》 CAS CSCD 北大核心 2008年第9期658-660,共3页 Shanghai Medical Journal
关键词 糖皮质激素 细胞外信号调节酶1/2 卵巢癌 Glucocorticoids Extracellular signal-reyulated kinase 1/2 Ovarian cancer
  • 相关文献

参考文献1

二级参考文献18

  • 1Liang -Nian Song.Gamma interferon down-regulates glucocorticoid receptor expression and attenuates hormone action in a human osteosarcoma cell line[J]. Endocrine . 1995 (10)
  • 2XuMJ,SongLN,WangZM.Effectsofglucocorticoidonproliferationanddifferentiationofhuamnovariancarcinomacells:3AO. AcadJSecMilUniv . 1999
  • 3ChungE,LeeKY,LeeYJ etal.GinsenosideRg1down regulatesglucocorticoidreceptorandsynergisticeffectswithcAMP. Steroids . 1998
  • 4KolS,BenSI,PayneDW etal.Glucocorticoidssuppressbasal (butnotinterleukinsupported)ovarianphospholipaseA2 activity:evidenceforglucocorticoidreceptormediatedregulation. MolCellendocrinol . 1998
  • 5Park MT,Cha HJ,Jeong JW,et al.Glucocorticoid receptorinduced down-regulation of MMP-9 by ginseng compnents, PD and PT contributes to inhibition of the invasive capacity of HT1080 human fibrosarcoma cells. Molecules and Cells . 1999
  • 6Braunschweiger PG,Ting HL,Schiffer LM,et al.Correlation between GR content and the antiproliferation effects of dex in experimental solid tumors. Cancer Research . 1983
  • 7McNally JG,Muller WG,Walker D,et al.The glucocorticoid receptor: rapid exchange with regulatory sites in living cells. Science . 2000
  • 8Tsai LC,Hung MW,Chang GC,et al.Apoptosis induced by the sodium butyrate gastric cancer TMK-1 cells. Anticancer Research . 2000
  • 9Glick RD,Medary I,Aronson DC,et al.The effects of serum depletion and dexamethasone on growth and differentiation of human neuroblastoma cell lines. Journal of Pediatric Surgery . 2000
  • 10Morita K,Ishimura K,Tsuruo Y,et al.Dexamethasone enhances serum deprivation -induced necrotic death of rat C6 glioma cells through activation of glucocorticoid receptors. Brain Research . 1999

共引文献11

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部