| MEK/ERK抑制剂影响胃癌细胞对5-FU敏感性及其机制的探讨 |
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| 引用本文： | 冯丹,刘静,曲秀娟,张晔,徐玲,曲晶磊,朱志图,刘云鹏. MEK/ERK抑制剂影响胃癌细胞对5-FU敏感性及其机制的探讨[J]. 中华肿瘤防治杂志, 2011, 18(5): 321-324 |
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| 作者姓名： | 冯丹 刘静 曲秀娟 张晔 徐玲 曲晶磊 朱志图 刘云鹏 |
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| 作者单位： | 1. 中国医科大学附属第一医院肿瘤内科,辽宁,沈阳,110001
2. 辽宁医学院附属第一医院肿瘤科,辽宁,锦州,121001 |
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| 基金项目： | 国家自然科学基金，辽宁省科技攻关计划 |
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| 摘 要： | 目的:探讨MEK/ERK特异性抑制剂PD98059在5-氟尿嘧啶(5-FU)抗胃癌细胞增殖中的作用。方法:应用5-FU与MEK/ERK抑制剂(PD98059)处理胃癌细胞,MTT法检测细胞增殖状态,流式细胞术检测细胞凋亡,蛋白质印迹法检测ERK和p-ERK的表达。结果:随着5-FU浓度的增加,5-FU对3种胃癌细胞系的增殖抑制率逐渐增大。5-FU作用MGC803细胞72 h的抑制率显著高于48和24 h,t值分别为16.477和25.349,P值分别为0.002和0.001。与对照相比,5-FU作用MGC803细胞48和72 h可引起显著的凋亡,t值分别为-20.576和-40.389,P值分别为0.015和0.001。5-FU处理胃癌MGC803细胞48 h,与对照相比pERK表达一过性下降然后升高。20μmol/L的PD98059联合5-FU作用48 h,可明显抑制pERK的表达,抑制率为22%;同时可明显增加细胞凋亡,增加率为20%。结论:MEK/ERK信号传导通路在5-FU作用胃癌细胞的过程中被激活,联合应用MEK/ERK信号通路抑制剂可部分逆转ERK的活化,增加胃癌细胞凋亡,从而增加胃癌细胞对5-FU的敏感性。
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| 关 键 词： | 胃肿瘤 5-氟尿嘧啶 有丝分裂原激活蛋白激酶 抑制剂 |
Mechanism and the sensitivity of MEK/ ERK inhibitor to 5-FU in gastric cancer cells |
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| FENG Dan,LIU Jing,QU Xiu-juan,ZHANG Ye,XU Ling,QU Jing-lei,ZHU Zhi-tu,LIU Yun-peng. Mechanism and the sensitivity of MEK/ ERK inhibitor to 5-FU in gastric cancer cells[J]. Chinese Journal of Cancer Prevention and Treatment, 2011, 18(5): 321-324 |
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| Authors: | FENG Dan LIU Jing QU Xiu-juan ZHANG Ye XU Ling QU Jing-lei ZHU Zhi-tu LIU Yun-peng |
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| Affiliation: | FENG Dan1,LIU Jing1,QU Xiu-juan1,ZHANG Ye1,XU Ling1,QU Jing-lei1,ZHU Zhi-tu2,LIU Yun-peng1 1.Department of Medical Oncology,First Affiliated Hospital,China Medical University,Shenyang 110001,P.R.China 2.Department of Medical Oncology,Liaoning Medical College,Jinzhou 121001,P.R.China |
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| Abstract: | OBJECTIVE: To investigate the effect of MEK inhibitor PD98059 in response of gastric cancer cell lines to 5-FU.METHODS: Human gastric cancer cell lines were used as cell models.5-FU,PD98059(inhibitor of MAPK Kinase-MEK/ERK),or 5-FU+PD98059 was added into the culture medium,the expressions of ERK and pERK were measured by Western blot,the growth of the cell lines were measured by MTT.The apoptosis ratio was detected using flow cytometer(FCM).RESULTS: The proliferative inhibition rate of 5-FU on three gastric... |
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| Keywords: | stomach neoplasms 5-fluorouracil mitogen activated protein kinase inhibitor |
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