抗ErbB2嵌合抗体chA21对SKBR3细胞的增殖抑制以及对PI3K/Akt和Erk1/2信号转导途径的影响  

Anti-proliferation role and effect on PI3K/Akt and Erk1/2 signal pathways of a chimeric anti-erbB2 antibody(chA21)on SKBR3 cells

作　　者：朱娟娟[1] 赵斌[2] 刘兢[3] 

机构地区：[1]安徽医科大学生物教研室,安徽合肥230032 [2]安徽医科大学药学院,安徽合肥230032 [3]中国科学技术大学生命科学学院细胞免疫学实验室,安徽合肥230027

出　　处：《中国药理学通报》2009年第11期1442-1445,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30570362);安徽省自然科学基金资助项目(No90413140);高校安徽省级优秀青年人才基金资助项目(No2009SQRZ043);安徽省高校青年教师科研资助项目(No2008jq1067);安徽医科大学校科研基金资助课题(No2007kjzj02;2008kj05)

摘　　要：目的检测抗ErbB2嵌合抗体chA21对高表达ErbB2乳腺癌细胞SKBR3的增殖抑制作用,并分析抗体对细胞膜上ErbB2分布以及对细胞PI3K/Akt和Erk1/2信号转导途径的影响,探讨chA21的抑癌机制。方法采用MTT检测chA21对SKBR3的增殖抑制作用,流式细胞术检测经chA21处理后细胞膜上ErbB2抗原的分布变化,Western blot检测抗体作用后对细胞PI3K/Akt和Erk1/2信号转导途径的影响。结果chA21可抑制SKBR3细胞的增殖,其作用呈剂量和时间依赖性。抗体作用后可下调细胞膜上ErbB2含量,并不同程度下调细胞的PI3K/Akt和Erk1/2的活化水平。结论chA21可抑制SKBR3细胞增殖,可能通过下调细胞膜上ErbB2分布而减少其介导的PI3K/Akt和Erk1/2信号转导途径的活化来实现的。Aim To study the inhibitory effect of anti-ErbB2 chimeric antibody chA21 on proliferation of human malignant breast cancer cell lines SKBR3 and explore its possible mechanisms through studying its effects on ErbB2 distribution and PI3K/Akt,Erk1/2 signal transduction.Methods The inhibitory effect of chA21 on SKBR3 was assessed by MTT assay.The effect of chA21 on distribution of ErbB2 on cell plasma membrane was determined by FACS（Fluorescence-activated cell sorting）analysis;p-Akt and p-Erk1/2 were detected by Western blot.Results The inhibitory rate of chA21 on SKBR3 cells in vitro increased in a dose and time dependent manner.Furthermore,it could down-regulate the distribution of ErbB2 on plasma membrane and decrease the activation of p-Akt and p-Erk1/2.Conclusions ChA21 can inhibit the proliferation of SKBR3 cell in vitro.Down-regulation ErbB2 on cell plasma membrane resulting in decreasing the activation of p-Akt and p-Erk1/2 may be one of the mechanisms of the inhibitory effect.

关 键 词：乳腺癌 SKBR3 ERBB2 嵌合抗体 PI3K/AKT ERK1/2 信号转导 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学] R329.24[医药卫生—基础医学]