肥大细胞调控IDO诱导的肺癌细胞转移-华东理工大学学报.PDF

DOI:10.14135/ki.1006-3080.20180402001 肥大细胞调控IDO 诱导的肺癌细胞转移 陈义杨， 刘建文 (华东理工大学生物反应器工程国家重点实验室,上海200237) 摘要：建立小鼠肥大细胞体外诱导体系。探究肥大细胞对肿瘤细胞侵袭转移能力的影响。Transwell 迁移和侵袭实验检测与肥大细胞共培养后2LL 细胞侵袭转移能力变化。实验结果表明：肥大细胞能够抑制 IDO 诱导的2LL 细胞侵袭转移能力。生物信息学分析发现TIMP1 能够抑制促肿瘤转移的MMP1 、MMP2 以及MMP9 的表达。Western blot 结果表明肥大细胞通过抑制STAT3 磷酸化减少IDO 的表达；并通过TIMP-1 信号通路抑制MMP2、MMP9 和VEGF 的表达。这些结果表明：肥大细胞通过抑制STAT3 信号通路磷酸 化调控IDO 表达和其下游TIMP 1/MMP2/MMP9 信号通路抑制2LL 细胞转移能力。 关键词：肥大细胞；IDO ；肿瘤转移；基质金属蛋白酶-9 ；基质金属蛋白酶抑制剂-1 中图分类号：R73-37 文献标志码：A Mast Cells Suppress IDO-induced Metastasis in Lung Carcinoma Cells CHEN Yi-yang, LIU Jian-wen （State Key Laboratory of Bioreactor Engineering Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China） Abstract:. The aim of this study was to investigate IDO expression and metastasis ability in lung carcinoma cells after co-culturing with mast cells. Mast cells were obtained from C57BL/6 mice (aged 4–6 weeks), and a cellular phenotype analysis was performed by flow cytometry. IDO expression in lung carcinoma cells was detected by real-time PCR and western blotting. Transwell migration and invasion assays were used to assess the metastasis function of lung carcinoma cells. Moreover, the effects of culturing lung carcinoma cells with mast cells on the STAT3 and TIMP/MMP signaling pathways were determined by western blotting. Then, metastatic-associated gene expression data were obtained from Gene Expression Omnibus database with 2 metastatic samples and 2 healthy samples. Then we used R software to analyze differentially expressed genes (DEGs) in metastatic colonization. IDO expression in lung