【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。更多还原

【Abstract】 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.更多还原