肿瘤相关巨噬细胞通过PI3K/Akt途径促进胰腺癌浸润迁移的研究  

Tumor-associated macrophages promoting invasion and migration of pancreatic cancer via PI3K/Akt signaling pathway

作　　者：叶会霖 叶良涛[1] 周雨[1] 周泉波[1] 林青[1] 李志花[1] 刘宜敏[1] 陈汝福[1] 

机构地区：[1]中山大学孙逸仙纪念医院胆胰外科,广州510120

出　　处：《中华普通外科学文献（电子版）》2015年第3期23-27,共5页Chinese Archives of General Surgery(Electronic Edition)

基　　金：国家自然科学基金资助项目(81000917;81370059)

摘　　要：目的研究PI3K/Akt信号通路对胰腺癌细胞PANC-1浸润迁移能力的影响,进一步探讨肿瘤相关巨噬细胞促进胰腺癌发生发展的分子机制。方法通过密度梯度离心法从健康成人外周血中分离单个核细胞,用IL-4体外诱导选择性激活的巨噬细胞(M2)。采用实时荧光定量PCR和Western blotting法检测胰腺癌PANC-1细胞PI3K、Akt mRNA和蛋白表达水平的变化,利用Transwell侵袭实验与划痕实验观察细胞浸润迁移能力的变化。结果体外模拟胰腺癌微环境,将胰腺癌PANC-1细胞与不同激活状态的巨噬细胞共培养,证明M2可显著上调胰腺癌PANC-1细胞PI3K、Akt的mRNA和蛋白水平,共培养20 h后可明显促进胰腺癌PANC-1细胞的浸润与迁移能力。结论肿瘤相关巨噬细胞可通过PI3K/Akt信号通路促进胰腺癌细胞的浸润与迁移。Objective To explore the influence of PI3K/Akt signaling pathway on invasive and mi-gratory ability of pancreatic cancer cell line PANC-1, and further investigate the molecule mechanism of tu-mor-associated macrophages＇promotion in the occurrence and development of pancreatic cancer. Methods Mononuclear cells were isolated from peripheral blood of healthy adults by density gradient centrifugation, and treated with IL-4 to obtain M2 in vitro. Expression of PI3K and Akt was evaluated by quantitative Real-time polymerase chain reaction and Western blotting. The ability of cellular invasion and migration was as-sessed by transwell chamber assay and wound healing assay. Results To simulate pancreatic cancer mi-croenvironment, we co-cultured pancreatic cancer PANC-1 cells and Ua or M2. The mRNA and protein lev-els of PI3K and Akt were remarkably increased analyzing by qRT-PCR and western blotting. In addition, transwell chamber assays and wound healing assays revealed that alternatively activated macrophages signif-icantly promoted the invasion and migration of PANC-1 cells in 20 h. Conclusion Tumor-associated macrophages may promote invasion and migration of pancreatic cancer cells via PI3K/Akt signaling pathway.

关 键 词：胰腺癌 肿瘤相关巨噬细胞 PI3K AKT 浸润迁移 

分 类 号：R735.9[医药卫生—肿瘤]