抗胰岛素样生长因子I型受体单克隆抗体m590抑制乳腺癌细胞增生和迁移  

Inhibition of breast cancer cell proliferation and migration by monoclonal antibody mS90 specific for insulin-like growth factor receptor type I

作　　者：符晓阳[1] 陈超[4] 潘华雄[2] 黄韬[3] 章美云[4] 郑鸿[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院血管外科,武汉430022 [2]华中科技大学同济医学院附属协和医院病理科,武汉430022 [3]华中科技大学同济医学院附属协和医院乳腺和甲状腺外科,武汉430022 [4]香港大学李嘉诚医学院微生物系艾滋病研究所

出　　处：《中华实验外科杂志》2012年第5期824-826,共3页Chinese Journal of Experimental Surgery

基　　金：香港大学应用研究种子基金资助项目

摘　　要：目的探讨抗胰岛素样生长因子I型受体（IGF—IR）抗体，m590，抑制乳腺癌细胞增生、迁移及其机制。方法免疫组织化学染色30例乳腺浸润性导管癌标本；免疫印迹法、免疫荧光细胞染色及其他试验检测m590对MCF-7细胞的作用及其机制。结果87％的乳腺浸润性导管癌离表达IGF．IR；m590抑制胰岛素样生长因子I（IGF—I）诱导的细胞外调节蛋白激酶（ERK）和蛋白激酶B（Akt）磷酸化以及细胞骨架蛋白（F—actin）和细胞骨架黏合班蛋白（Vinculin）在细胞内的分布，使细胞增生、迁移和黏附分别降低至58％、56％和55％，并促进细胞凋亡；M590与赫赛汀联用抑制IGF—I诱导的ERK和Akt磷酸化，使细胞增生降低76％。结论nr590是一个有效抑制乳腺癌细胞增生、迁移和黏附的抗IGF—IR抗体。Objective To investigate the mechanism（s） that a human-mouse chimeric monoclonal anti-insulin-like growth factor receptor type I （IGF-IR） antibody, m590, inhibits breast cancer cells prolif- eration and migration. Methods Binding of m590 to IGF-IR in 30 breast cancer samples was detected by using immunohistochemistry. Western blotting, immunocytofluorescence and other tests were used for ana- lyzing the effects of m590 on breast cancer cells （ MCF-7 ） proliferation, survival, adhesion and migration as well as signaling pathways. Results m590 specifically bound to IGF-IR was overexpressed in invasive ductal carcinoma of the breast （87% of cases ）. Treatment of MCF-7 cells with m590 significantly suppressed IGF-I-induced phosphorylation of ERK and Akt, which led to reduced cell proliferation by 58% and increased apoptosis, m590 also inhibited IGF-I-induced polymerization of F-actin and relocation of vin-culin in cell edge, resulting in dramatically decreased cell migration by 56% and cell adhesion by 55%. Furthermore, herceptin in combination with m590 synergistically inhibited IGF-IR-induced phosphorylation of ERK and AKT, and decreased MCF-7 cells proliferation by 76% as compared with IGF-I treatment a- lone. Conclusion m590 is an effective anti-IGF-IR antibody and may have the potential in clinical use for diagnosis and treatment of breast cancer.

关 键 词：乳腺癌 胰岛素样生长因子I型受体 增生 迁移 

分 类 号：R734.2[医药卫生—肿瘤]