内质网应激反应调控三阴性乳腺癌细胞对西妥昔单抗耐受的研究

摘要

目的：研究内质网应激反应(UPR)调控三阴性乳腺癌细胞对西妥昔单抗(Cetuxmab)耐受的机制,明确Cetuxmab的体内外抗三阴性乳腺癌作用。方法：将实验分为SiRNA组和对照SiRNA组,采用流式细胞仪检测细胞的抑制率,western blot检测GRP78的表达量,研究西妥昔单抗体外抑制乳腺癌细胞增殖的作用；采用荷瘤裸鼠移植模型研究西妥昔单抗体外抑制乳腺癌细胞增殖的作用。结果：RNA干扰组的抑制率明显高于非干扰组；而RNA干扰组的表达率明显低于于非干扰组。表达率越高,抑制率越低。结论：体内外试验均表明西妥昔单抗对三阴性乳腺癌有治疗作用,但受到内质网反应的调节, GRP78有可能成为三阴性乳腺癌患者治疗的新的靶点。%Objective:To study the endoplasmic reticulum stress response regulation of triple negative breast cancer cells' tolerance mechanism to cetuximab in vitro and in vivo,study the role of Cetuxmab to the triple negative breast cancer cells.Methods:Experiment was divided into SiRNA group and control SiRNA group,the use of flow cytometry inhibition and Western blot detection of GRP78 expression,study of cetuximab in vitro inhibition of proliferation of breast cancer cells; tumor-bearing nude mice transplantation model study of cetuximab in vitro inhibition of proliferation of breast cancer cells. Results:The inhibition of RNA interference group was significantly higher than non-interference group;expression of RNA interference group was significantly lower than in the non-interference group.The expression rate of the higher inhibition rate is lower.Conclusion:Vitro and vivo tests showed that cetuximab triple negative breast cancers have a therapeutic effect,but subject to the regulation of the response of the endoplasmic reticulum,GRP78 may become a new target for treatment of triple negative breast cancer patients.