MAPK信号通路对地塞米松抑制Jurkat细胞增殖及诱导凋亡的影响  

Effect of MAPK signal pathway on proliferation and apoptosis inhibited and induced by dexamethasone in Jurkat cells

作　　者：周焕娟[1] 何莉[1] 

机构地区：[1]中国医科大学附属第一医院儿科,沈阳110001

出　　处：《实用药物与临床》2016年第8期937-941,共5页Practical Pharmacy and Clinical Remedies

基　　金：辽宁省高等学校科研项目计划(2008821);辽宁省博士启动基金资助项目(20081050)

摘　　要：目的研究丝裂原活化蛋白激酶(MAPK)信号通路对地塞米松(Dexamethasone,DEX)诱导急性淋巴细胞白血病Jurkat细胞凋亡及抑制细胞增殖的影响。方法观察地塞米松、PD98059、SP600125、SB203580及地塞米松分别联合PD98059、SP600125、SB203580对Jurkat细胞增殖及凋亡的抑制作用。以急性淋巴细胞白血病Jurkat细胞为研究对象,应用WST-1法检测细胞的增殖活力;流式细胞术分析细胞凋亡。结果地塞米松对Jurkat细胞24 h和48 h抑制细胞增殖50%的药物浓度(IC50)分别为829、335μM。100μM以上地塞米松以时间、剂量依赖方式抑制Jurkat细胞增殖;地塞米松分别联合PD98059、SP600125可增加对Jurkat细胞增殖的抑制效应,联合SB203580对地塞米松抑制Jurkat细胞增殖无影响。10μM地塞米松联合20μM PD98059可显著增加地塞米松诱导Jurkat细胞凋亡的作用,细胞凋亡率由8.5%升至28.4%。结论急性淋巴细胞白血病Jurkat细胞为糖皮质激素耐药细胞。阻断p38MAPK对地塞米松抑制Jurkat细胞增殖无明显影响。阻断ERK、JNK信号通路均可增强地塞米松对Jurkat细胞的杀伤作用,达到逆转Jurkat细胞对地塞米松的耐药。急性淋巴细胞白血病Jurkat细胞糖皮质激素耐药可能与ERK、JNK通路的活化有关。Objective To study the effect of mitogen-activated protein kinase （MAPK） signal pathway on the inhibition of proliferation and apoptosis induced by dexamethasone in glucocorticoid-resistance Jurkat cell line. Methods The inhibition of proliferation and apoptosis of Jurkat cell, after being treated respectively with dexamethasone, PD98059, SP600125, SB203580 and dexamethasone combined with PD98059, SP600125 and SB203580,was observed. The proliferation and apoptosis was detected by WST-1 assay and flow cytometry respectively using Jurkat cell as the subjects. Results The 24 h and 48 h ICs0 of dexamethasone to Jurkat cell was 829 p^M and 335 p.M. Dexamethasone inhibited the proliferation of Jurkat cell in a dose-/time- dependent manner when the concentration was more than 100 p^M. Dexamethasone combined with PD98059 and SP600125 could enhance the inhibition effect of dexamethasone, but no significant inhibition effect was observed when it was combined with SB203580. Dexamethasone 10 ixM com- bined with PD98059 20 p^M could significantly promote the apoptosis induced by dexamethasone in Jurkat cell. The ap- optosis rate rose from 8.5 % to 28.4%. Conclusion Acute lymphoblastic leukemia Jurkat cell is resistant to glucocor- ticoid. Inhibiting p38MAPK has no obvious influence on the proliferation of Jurkat cell, while inhibiting ERK or JNK signal pathway can enhance the effect of dexamethasone on Jurkat cell, thus reversing the resistance of Jurkat to dexam- ethasone. The activation of ERK and JNK signal pathway plays an important role in glucocorticoid resistance of acute lymphoblastic leukemia.

关 键 词：丝裂原活化蛋白激酶信号通路 地塞米松 耐药 凋亡 JURKAT细胞 

分 类 号：R96[医药卫生—药理学]