基因工程抗体联合紫杉醇对BT474细胞的促凋亡作用  

Apoptotic effect of the combined treatment of engineered antibody with paclitaxel on BT474 cells

作　　者：尹荟菁[1] 程联胜[2] 段家龙[1] 

机构地区：[1]安徽农业大学生命科学学院分子遗传学实验室,安徽合肥230036 [2]中国科学技术大学生命科学学院细胞与分子免疫学实验室,安徽合肥230027

出　　处：《细胞与分子免疫学杂志》2007年第3期260-263,共4页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金资助项目(30400078);安徽省自然科学基金资助项目(050430201)

摘　　要：目的:探讨抗p185c-erbB-2/neu基因工程抗体联合紫杉醇促进p185过表达的人乳腺癌细胞系BT474凋亡的效应及其机制。方法:采用MTS法检测基因工程抗体联合紫杉醇对BT474细胞增殖的抑制作用。用AnnexinV-FITC/PI法检测BT474细胞的凋亡率;以流式细胞术(FCM)分析DNA含量及细胞周期分布;用EMSA分析NF-κB的活化水平。结果:基因工程抗体联合紫杉醇对BT474细胞增殖的抑制作用具有协同效应,并可诱导细胞凋亡,将细胞阻滞在G1期;并可显著抑制BT474细胞中NF-κB的活化。结论:紫杉醇诱导乳腺癌细胞BT474凋亡的同时,可活化NF-κB。基因工程抗体联合紫杉醇是通过抑制NF-κB的活化而增强紫杉醇诱导癌细胞凋亡的作用。AIM.. To explore the apoptotic effect of the combined treatment of anti-p185^c-erbB-2/neu engineered antibody with paclitaxel on p185-overexpressing human malignant breast cancer cell lines BT474 and to study its emerging mechanism. METHODS： The prohibitory effect of engineeded antibody plus paclitaxel on BT474 cells was assessed by MTS assay. The number of apoptotic cells was detected by Annexin V-FITC/PI. DNA content and cell cycle distribution were determined by FCM; DNA-binding activity of NF-KB was demonstrated by EMSA. RESULTS： Anti- p185c-erbB-2/neu engineered antibody plus paclitaxel resulted in synergistic effect on proliferative inhibiton of BT474 cells, which was mediated via apoptotic induction and caused cell cycle to arrest at G1 phase remarkably. Furthermore, the combined treatment of the engineered antibody with paclitaxel effectively suppressed the activation of NF-KB in BT474 cells. CONCLUSION： The combined treatment of anti- p185^c-erbB-2/neu engineered antibody with paclitaxel rendered p]85-overexpressing human malignant breast cancer cells BT474 more susceptible to paclitaxel-induced apoptosis by the effective suppression of NF-κB activation.

关 键 词：p185^c-erbB-2/neu 基因工程抗体 紫杉醇 凋亡 NF-ΚB 乳腺癌 

分 类 号：R737.9[医药卫生—肿瘤]