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

作　　者：徐明娟[1] 惠宁[1] 

机构地区：[1]第二军医大学附属长海医院妇产科,上海200433

出　　处：《上海医学》2008年第9期658-660,共3页Shanghai Medical Journal

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.

关 键 词：糖皮质激素 细胞外信号调节酶1/2 卵巢癌 

分 类 号：R737.31[医药卫生—肿瘤]