CAJ | 학술논문

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高表达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 m590 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.
목적 탐토항이도소양생장인자Ⅰ형수체(IGF-IR)항체,m590,억제유선암세포증생、천이급기궤제.방법 면역조직화학염색30례유선침윤성도관암표본；면역인적법、면역형광세포염색급기타시험검측m590 대MCF-7세포적작용급기궤제.결과 87％적유선침윤성도관암고표체IGF-IR；m590억제이도소양생장인자Ⅰ(IGF-I)유도적세포외조절단백격매(ERK)화단백격매B(Akt)린산화이급세포골가단백(F-actin)화세포골가점합반단백(Vinculin)재세포내적분포,사세포증생、천이화점부분별강저지58％、56％화55％,병촉진세포조망；M590 여혁새정련용억제IGF-I유도적ERK화 Akt 린산화,사세포증생강저 76％.결론 m590 시일개유효억제유선암세포증생、천이화점부적항IGF-IR항체.
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 proliferation 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 analyzing 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 vinculin 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 alone.Conclusion m590 is an effective anti-IGF-IR antibody and may have the potential in clinical use for diagnosis and treatment of breast cancer.