EGR-1的表达对乳腺癌细胞株耐药的调节作用  

Up-regulated EGR-1 can increase chemotherapy sensitivity on adriamycin resistance of breast carcinoma cells

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作  者:孔灵玲[1] 崔文[1] 肖兰[2] 王旭[1] 张国安[1] 姜晓刚[1] 魏红[1] 

机构地区:[1]济宁医学院基础学院,山东日照276826 [2]中山大学附属第三医院,广东广州510630

出  处:《济宁医学院学报》2009年第3期153-155,共3页Journal of Jining Medical University

基  金:山东省教育厅资助课题(Y07YD17);卫生厅十一五医药科技卫生计划(2007 HZ018)

摘  要:目的探讨转录因子EGR-1对人乳腺癌阿霉素耐药细胞MCF-7/Adr耐药的调节作用。方法采用脂质体转染法将EGR-1质粒转入细胞,Annexin V-FITC/PI双标流式细胞术、MTT法和Western印迹分别检测MCF-7/Adr细胞早晚期凋亡、细胞增殖活性。结果细胞稳定转染EGR-1质粒后,与阴性对照组和空载体组比较,细胞凋亡率(41.43±2.34)%高于阴性对照组(4.32±0.87)%及pcDNA3.1空载体转染(5.28±1.46)%(P<0.05);在一定阿霉素药物浓度范围内,MCF-7/Adr细胞存活率抑制率明显下降(P<0.05);West-ern印迹检测见MCF-7/Adr-EGR-1细胞中Caspase-3蛋白均较转染前明显增加,而p-gp蛋白质水平较转染前明显下降(P<0.05)。结论上调EGR-1表达能有效逆转乳腺癌细胞阿霉素耐药性,其作用机制可能与EGR-1上调耐药细胞中Caspase-3的水平、诱导细胞发生凋亡相关。Objective To investigate the chemotherapy sensitivity of how transcription factor EGR-1 influence the adriamycin resistance of breast carcinoma cells. Methods We transfected the expression type human EGR-1 plasmid to MCF-7/Adr cells to enhance the expression of EGR-1. Then double stain with Annexin-V-FITC/PI to detect cell apoptosis by the flow cytometry(FCM). MCF-7/Adr cell viability was determined via MTT method. Caspase-3 and p-gp protein were detected by Western blot. Results After stable transfected with pcDNA3.1/EGR-1 plasmid,the apoptosis efficiency was much higher in EGR-1 transfected cells(41.43- 2.34)% than that in pcDNA3.1 empty vector (5.28 - 1.46) % and negative control group (4. 32 - 0.87) % ( P 〈 0.05) ; In the presence of different concentrations of adriamycin, MCF-7/Adr cells viability was significantly decreased after transfection. The expression of Caspase-3 protein of EGR-1 transfected group in MCF-7/Adr cells was significantly increased,and the expression of p-gp protein was significantly decreased. Conclusion It was showed that the up-expression of EGR-1 can effectively reverse adriamycin resistance in MCF-7/Adr cells. It is may be related to up-regulation EGR-1 increasing Caspase-3 level and inducing cell apoptosis.

关 键 词:转录因子EGR-1 阿霉素耐药 乳腺癌 凋亡 

分 类 号:R73-35[医药卫生—肿瘤]

 

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