甘精胰岛素和人胰岛素对人乳腺癌MDA-MB-231细胞的增殖作用  

Effect of insulin glargine and human insulin on proliferation of a human breast cancer cell line MDA-MB-231

作　　者：刘珊英[1] 李焱[2] 潘秋辉[1] 魏菁[1] 梁颖[2] 傅玉如[1] 梁蔚文[1] 林天歆[1] 

机构地区：[1]中山大学附属第二医院林百欣医学研究中心,广东广州510120 [2]中山大学附属第二医院内分泌科,广东广州510120

出　　处：《中国药理学通报》2010年第6期719-722,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30671974);广东省自然科学基金资助项目(No4009408;No6021329)

摘　　要：目的探讨甘精胰岛素(insulin glargine)和人胰岛素(human insulin)对人乳腺癌细胞株MDA-MB-231增殖的影响及细胞外信号调节激酶(ERK)的调节作用。方法使用不同浓度的甘精胰岛素和人胰岛素刺激人乳腺癌MDA-MB-231细胞株,检测不同时间段的细胞增殖作用,探讨抑制ERK1/2激活对细胞增殖的影响。使用cell counting kit-8(CCK-8)试剂检测细胞增殖,流式细胞术检测细胞周期分布。结果甘精胰岛素和人胰岛素在1、10、100IU.L-1刺激MDA-MB-231细胞96h后均可轻度促进MDA-MB-231细胞增殖,相同条件下甘精胰岛素和人胰岛素的促增殖效应无差异。甘精胰岛素与人胰岛素以10IU.L-1分别刺激48、72、96h后两药均诱导细胞增殖,比较两种药物间增殖效应的差异无统计学意义。甘精胰岛素和人胰岛素均使S+G2/M期细胞比例增加,但两处理组间差异无显著性。ERK1/2抑制剂PD98059可抑制MDA-MB-231细胞增殖;但PD98059不影响甘精胰岛素和人胰岛素对MDA-MB-231细胞增殖的促进作用。结论甘精胰岛素和人胰岛素对人乳腺癌细胞株MDA-MB-231增殖有类似的轻度促进作用,该作用不依赖于ERK的激活。Aim To investigate the effect of insulin glargine and human insulin on proliferation of a human breast cancer cell line MDA-MB-231 and the role of ERK in the process.Methods MDA-MB-231 cells were incubated with insulin glargine and human insulin at different concentrations and for different time courses.A specific ERK1/2 inhibitor,PD98059,was used either alone or in combination with insulin glargine or human insulin to test the involvement of ERK pathway in cell growth.Cell proliferation was evaluated using cell counting kit-8 reagents.Cell cycle distribution was analyzed by flow cytometry.Results Both insulin glargine and human insulin dose-dependently enhanced MDA-MB-231 cell proliferation at the concentrations from 1 to 100 IU·L-1 after treatment for 96 h.At the concentration of 10 IU·L-1,both drugs promoted cell growth at 48,72,and 96 h.The percentage of S＋G2/M cells was significantly increased in both insulin glargine and human insulin treated groups as compared to untreated controls.No significant difference was observed between insulin glargine and human insulin in their effects on cell proliferation and cell cycle distribution.Cell proliferation was significantly inhibited by PD98059.However,in the presence of PD98059,both drugs still promoted cell proliferation significantly as compared to untreated controls.Conclusions Insulin galrgine and human insulin similarly promote proliferation of MDA-MB-231 cells independent of ERK activation.

关 键 词：甘精胰岛素 人胰岛素 ERK PD98059 人乳腺癌细胞 MDA-MB-231 

分 类 号：R329.24[医药卫生—人体解剖和组织胚胎学] R345.57[医药卫生—基础医学]