乳腺癌耐药性中MAPK信号转导通路与EGR-1关系的研究  

Targeting of p38 Mitogen-Activated Activity to Early Growth Response Gene 1 (EGR-1) in the Human Breast Carcinoma MCF-7/Adr Cells

作　　者：崔文[1] 孔灵玲[1] 肖兰[2] 王旭[1] 张国安[1] 

机构地区：[1]济宁医学院病理学教研室 [2]中山大学附属第三医院妇产科博士后流动站

出　　处：《济宁医学院学报》2009年第1期1-3,共3页Journal of Jining Medical University

基　　金：山东省教育厅课题(2007YD17);卫生厅十一五医药科技卫生计划课题(2007HZ18)

摘　　要：目的探讨乳腺癌细胞阿霉素耐药中p38MAPK通路与EGR-1活性的关系。方法用流式细胞术、四甲基偶氮唑蓝(MTT)、RT-PCR及Western Blot等方法分别检测SB203580(15μmol/L)干预后细胞的凋亡、细胞内阿霉素浓度及细胞对阿霉素敏感性的改变;EGR-1 mRNA表达及p-gp、磷酸化p53蛋白及p38蛋白表达情况。结果经SB203580(15μmol/L)干预,流式细胞仪检测见MCF-7/Adr细胞发生显著凋亡,并呈一定时间依赖性;细胞内阿霉素浓度显著增加;MCF-7/Adr细胞对阿霉素药物的耐受性显著降低;伴随p38MAPK通路活性抑制和EGR-1 mRNA表达增加,磷酸化p53蛋白表达显著上调,而p-gp蛋白显著下调。结论提示p38MAPK通路与乳腺癌细胞阿霉素耐药密切相关,p38MAPK通路调控的EGR-1激活参与乳腺癌细胞阿霉素耐药的形成。Objective To investigate the relationship between the activity of early growth response gene 1 （EGR- 1 ） and p38MAPK pathway in the adriamyein resistance of breast carcinoma ceils. Methods Using p38MAPK inhibitor SB203580 to analyze the effect on the cell apoptosis through FITC - Annexin - V/PI double staining. The concentration of adriamycin was detected by the flow cytometry （FCM）. 50% inhibition concentration （IC50） of adriamycin on MCF - 7/Adr cells was determined by MTr method. EGR - 1mRNA were assessed by RT - PCR. The expressed of p - gp, phosphorylated p53 and p38 were detected by Western blot. Results SB203580 could remarkably facilitate the apoptosis of MCF -7/Adr cells, and the cell apoptosis was in a time - dependent manner. Inhibition of p38MAPK pathway could increase cellular adriamycin accumulation of MCF-7/ Adr cells, and the IC50 of adriamycin for MCF - 7/Adr cells was decreased significantly. SB203580 significantly increased the cellular phosphorylated p53 protein level, but decreased the p - gp protein level in MCF - 7/Adr cells. Conclusion There has a closely relationship between p38MAPK pathway and the adriamycin resistance of breast carcinoma cells. The activation of EGR - 1 mediated by p38MAPK pathway plays a critical role in adriamycin resistance of breast carcinoma cells.

关 键 词：乳腺癌 P38MAPK通路 EGR-1 阿霉素耐药 

分 类 号：R735.2[医药卫生—肿瘤] R737.9[医药卫生—临床医学]