选择性激活巨噬细胞通过JAK2/STAT3途径促进胰腺癌SW1990细胞侵袭迁移

Alternatively-activated macrophages promote invasion and migration of pancreatic cancer SW1990 cells via JAK2/STAT3 signaling pathway

目的:探讨JAK2/STAT3通路对胰腺癌SW1990细胞侵袭迁移能力的影响,研究肿瘤相关巨噬细胞(TAMs)促进胰腺癌演进的机制。方法:通过密度梯度离心法获取健康成人外周血单个核细胞,采用IL-4体外诱导选择性激活巨噬细胞(M2),模拟胰腺癌微环境中的TAMs,并将不同激活状态的巨噬细胞与胰腺癌SW1990细胞进行共培养。采用q-PCR和western blotting实验检测胰腺癌SW1990细胞JAK2、STAT3 m RNA与蛋白水平的变化,划痕实验和Transwell实验分别检测细胞迁移与侵袭能力的变化。结果:M2可明显上调胰腺癌SW1990细胞JAK2、STAT3的m RNA(P<0.05)与蛋白水平(P<0.05),共培养32 h后可显著促进胰腺癌SW1990细胞的横向迁移(P<0.05)和纵向侵袭能力(P<0.05)。结论:M2可通过JAK2/STAT3信号通路促进胰腺癌SW1990细胞的侵袭和迁移。

Objective： To investigate the effects of JAK2 / STAT3 signaling pathway on the invasion and migration of pancreatic cancer SW1990 cells, and study the specific mechanism of tumor-associated macrophages（TAMs） in promoting the tumorigenesis and progression of pancreatic cancer. Methods： Perip- heral blood mononuclear cells of healthy aduhs were isolated by means of density gradient centrifugation, alternatively-activated macrophages were induced by the stimulation of interleukin-4 in vitro, and pancreatic cancer SW1990 cells and macrophages were co-cultured with differentiate activated states in order to simulate TAMs in the pancreatic cancer microenvironment. The mRNA and protein levels of JAK2 and STAT3 were evaluated by real-time q-PCR and western blotting. The ability of migration and invasion was detected by wound healing assay and transwell chamber assay respectively. Results： The mRNA and protein levels of JAK2 and STAT3 were significantly in creased evaluated by qRT-PCR and westernblotting （P〈0.05）. Wound healing assays and transwell chamber assays indicated that alternatively activated macrophages obviously promoted the migration and invasion of SW1990 cells after 32 h＇s co-culture （P〈 0.05）. Conclusion： Alternatively-activated macrophages can promote the ability of migration and invasion of pancreatic cancer SW1990 cells via JAK2 / STAT3 signaling pathway.