PI3K和MEK抑制剂抑制选择性激活的巨噬细胞促乳腺癌细胞浸润迁移的研究  

Study on Inhibitors of PI3K/MEK Prevent Alternatively Activated Macrophages from Promoting Breast Cancer Cell Invasion and Migration

作　　者：陈静琦[1] 曾波航[1] 朱必胜[1] 侯开连[1] 

机构地区：[1]广州医学院第二附属医院肿瘤科,广州510260

出　　处：《肿瘤防治研究》2013年第3期221-225,共5页Cancer Research on Prevention and Treatment

基　　金：国家自然科学基金资助项目(81172537);广州市属高校科技计划项目资助课题(08A080)

摘　　要：目的探讨选择性激活的巨噬细胞(M2)促进乳腺癌浸润迁移的分子机制,为治疗乳腺癌提供新的分子靶点。方法用密度梯度离心法,从健康成人外周血中分离单个核细胞,体外诱导选择性激活巨噬细胞(M2)。用Western blot的方法检测M2对乳腺癌信号分子的激活;用浸润迁移实验和划痕实验检测PI3K和ERK抑制剂对M2促乳腺癌迁移的抑制作用。结果模拟乳腺癌微环境,把M2与乳腺癌MDA-MB-231细胞共培养,证明PI3K抑制剂LY294002和MEK抑制剂U0126作用于乳腺癌细胞,可以在6、12 h抑制M2对乳腺癌PI3K/ERK的激活;两种抑制剂可以抑制M2促进乳腺癌浸润迁移的作用。结论 PI3K和MEK抑制剂可以抑制M2促进乳腺癌浸润迁移,PI3K/ERK可以成为抑制M2作用的新靶点。Objective To interpret new molecular targets for breast cancer therapy and investigated the molecular mechanism of alternatively activaed macrophages（M2）′s promotion in breast cancer invasion and migration.Methods Mononuclear cells were isolated from peripheral blood of normal adults by density gradient centrifugation,and alternatively activated M2 in vitro.Activation of M2 to breast cancer signal molecules was detected by Western blot.The inhibition function of PI3K/ERK inhibitors to（M2）′s promotion in breast cancer migration was evaluated by invasion assay and wound assay.Results To simulate breast cancer microenvironment,we co-cultured M2 and breast cancer MDA-MB-231 cells.In the co-cultur system,the inhibitors,LY294002 of PI3K,U0126 of MEK,inhibiting（M2）′s activation to breast cancer PI3K/ERK in 6,12 h.The two inhibitors can prevent（M2） from promoting breast cancer invasion and migration.Conclusion The inhibitors of PI3K/MEK prevent M2 from promoting breast cancer invasion and migration.They can be new targets of breast cancer therapy.

关 键 词：乳腺癌 选择性激活的巨噬细胞 PI3K ERK 浸润迁移 

分 类 号：R737.9[医药卫生—肿瘤]