中国医学科学院学报

高级检索
中国医学科学院学报

中国医学科学院学报 ›› 2013, Vol. 35 ›› Issue (5): 530-534.doi: 10.3881/j.issn.1000-503X.2013.05.009

• 论著 • 上一篇    下一篇

在肿瘤细胞模型中联合应用磷脂酰肌醇3激酶/蛋白酶B通路抑制剂BEZ235和细胞外调解蛋白激酶/丝裂原活化蛋白激酶通路抑制剂U0126的效果

陈欣欣1, 张舒2, 石玉镯1   

  1. 1中国医学科学院 北京协和医学院 基础学院生理系,北京 100005; 
    2中国医学科学院 北京协和医学院 北京协和医院皮肤科,北京 100730
  • 收稿日期:2013-05-08 出版日期:2013-11-01 发布日期:2013-11-01
  • 通讯作者: 陈欣欣 电话:010-69156468,电子邮件:chenxinx@hotmail.com E-mail:chenxinx@hotmail.com
  • 基金资助:

    国家自然科学基金(81101516)

Efficacy of Combination Treatment of the Inhibitor of Phosphatidyl Inositol-3-Kinase/Protein Kinase B Pathway BEZ235 and the Inhibitor of Extracellular Regulated Protein Kinase/Mitogen-activated Protein Kinase Pathway U0126 in A Tumor Cell Model

CHEN Xin-xin1,ZHANG Shu2,SHI Yu-zhuo1   

  1. 1 Department of Physiology,Institute of Basic Medical Sciences,CAMS and PUMC,Beijing 100005,China;
    2 Department of Dermatology,PUMC Hospital,CAMS and PUMC,Beijing 100730,China
  • Received:2013-05-08 Online:2013-11-01 Published:2013-11-01
  • Contact: CHEN Xin-xin Tel:010-69156468,E-mail:chenxinx@hotmail.com E-mail:chenxinx@hotmail.com
  • Supported by:

    Supported by the National Natural Sciences Foundation of China(81101516)

摘要:

目的 探讨通过联合应用磷脂酰肌醇3激酶(PI3K)/蛋白酶B(AKT)通路抑制剂BEZ235和细胞外调解蛋白激酶(ERK)通路抑制剂U0126抑制膜受体酪氨酸激酶/PI3K/AKT/雷帕霉素靶蛋白(mTOR)通路与ERK/丝裂原活化蛋白激酶通路对细胞增殖的影响。方法 以磷酸酶和张力蛋白同源物缺失(PTEN-/-)的小鼠胚胎成纤维细胞(MEF)系作为研究对象,联合应用PI3K、mTOR双重抑制剂BEZ235及ERK激酶抑制剂U0126,通过MTT和Western blot方法检测药物对细胞增殖的影响。结果 BEZ235及U0126对PTEN-/-MEF细胞均有抑制作用,二者半数抑制浓度分别为6.257 nmol/L及22.85 μmol/L。但联合应用BEZ235与U0126,二者表现为拮抗的作用方式。结论 在PTEN缺失的细胞系中或PTEN突变的肿瘤的联合靶向治疗中,不推荐应用BEZ235与U0126联合使用。

关键词: 膜受体酪氨酸激酶/磷脂酰肌醇3激酶/蛋白酶B/雷帕霉素靶蛋白通路, 细胞外调解蛋白激酶/丝裂原活化蛋白激酶通路, BEZ235, U0126

Abstract:

Objective To study the inhibitory effect of the dual usage of BEZ235 and U0126,the inhibitor of phosphatidyl inositol-3-kinase/protein kinase B pathway and extracellular regulated proteinkinase/mitogen-activated protein kinase pathway,respectively,on cell proliferation.Methods Phosphatase and tensin homolog knockout mouse embryonic fibroblast(PTEN-/-MEF)cell lines were used as the cellular model for malignant tumors.BEZ235,the dual inhibitor of phosphatidyl inositol-3-kinase and mammalian target of rapamycin,and U0126,the inhibitor of mitogen-activated protein kinase were used to treat the cells individually and in a combination manner.The inhibitory effects to cell proliferation were monitored by MTT.Results Both BEZ235 and U0126 suppressed PTEN knockout cell proliferation,and their half inhibitory concentrations were 6.257 nmol/L and 22.85 μmol/L,respectively.However,the combination treatment of the two drugs showed antagonistic rather than synergistic effect on cell proliferation.Conclusion BEZ235 and U0126 are not suitable for a combined target therapy regimen.

Key words: receptor tyrosine kinase/phosphatidyl inositol-3-kinase/protein kinase B/mammalian target of rapamycin pathway, extracellular regulated protein kinase/mitogen-activated protein kinase pathway, BEZ235, U0126