| 二甲双胍通过巨噬细胞抑制食管癌TE-1细胞的侵袭和迁移 |
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| 引用本文： | 李雪曼,熊 飞,刘 冲,陈 康,吴平尚,张 倬. 二甲双胍通过巨噬细胞抑制食管癌TE-1细胞的侵袭和迁移[J]. 现代肿瘤医学, 2022, 0(22): 4040-4046. DOI: 10.3969/j.issn.1672-4992.2022.22.003 |
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| 作者姓名： | 李雪曼 熊 飞 刘 冲 陈 康 吴平尚 张 倬 |
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| 作者单位： | 武汉市第三医院，湖北 武汉 430070 |
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| 基金项目： | 湖北省武汉市卫生健康委一般项目（编号:WX21Z07） |
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| 摘 要： | 目的:探究二甲双胍是否通过巨噬细胞抑制食管癌TE-1细胞的侵袭迁移及其可能的分子机制。方法:100 ng/mL PMA诱导THP-1巨噬细胞。取对数生长期TE-1细胞和巨噬细胞，分别用最终浓度为0.5 mmol/L、1 mmol/L和2 mmol/L二甲双胍处理，Western blot检测MMP9、VEGF蛋白表达水平，ELISA检测细胞TNF-α和IL-8浓度，筛选二甲双胍最佳作用浓度（2 mmol/L）。分别用100 ng/mL LPS、2 mmol/L二甲双胍、100 ng/mL LPS+2 mmol/L二甲双胍处理巨噬细胞制备条件培养基。将TE-1细胞分为4组:对照组、LPS-条件培养基组（LPS组）、二甲双胍-条件培养基组（Met组）和LPS+二甲双胍-条件培养基组（LPS+Met组）。划痕实验观察各组细胞迁移能力。Transwell小室检测细胞侵袭能力。Western blot检测各组细胞VEGF、E-cad、Vimentin和NEDD9的表达。ELISA检测各组细胞TNF-α和IL-8浓度。结果:与对照组相比，二甲双胍可显著降低TE-1细胞和巨噬细胞中MMP9、VEGF、TNF-α和IL-8水平（P＜0.05），且呈剂量依赖性。二甲双胍可显著抑制TE-1细胞迁移和侵袭（P＜0.05），显著抑制VEGF、Vimentin和NEDD9蛋白表达（P＜0.05），促进E-cad蛋白表达（P＜0.05）；显著降低TE-1细胞中TNF-α和IL-8水平（P＜0.05）。结论:二甲双胍可通过巨噬细胞降低食管癌TE-1细胞NEDD9的表达，抑制食管癌细胞侵袭迁移。
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| 关 键 词： | 二甲双胍 食管癌 巨噬细胞 NEDD9 侵袭 迁移 |
Metformin inhibits the invasion and migration of esophageal cancer TE-1 cells through macrophages |
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| LI Xueman,XIONG Fei,LIU Chong,CHEN Kang,WU Pingshang,ZHANG Zhuo. Metformin inhibits the invasion and migration of esophageal cancer TE-1 cells through macrophages[J]. Journal of Modern Oncology, 2022, 0(22): 4040-4046. DOI: 10.3969/j.issn.1672-4992.2022.22.003 |
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| Authors: | LI Xueman XIONG Fei LIU Chong CHEN Kang WU Pingshang ZHANG Zhuo |
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| Affiliation: | Third Hospital of Wuhan,Hubei Wuhan 430070,China. |
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| Abstract: | Objective:To investigate whether metformin inhibits the invasion and metastasis of esophageal cancer TE-1 cells through macrophages and its possible molecular mechanism.Methods:THP-1 macrophages were induced by 100 ng/mL PMA.TE-1 cells and macrophages at logarithmic growth stage were treated with metformin at final concentrations of 0.5 mmol/L,1 mmol/L and 2 mmol/L,respectively.Western blot was used to detect the protein expression levels of MMP9 and VEGF,and ELISA was used to detect the concentrations of TNF-α and IL-8.The optimal concentration of metformin (2 mmol/L) was selected.Macrophages were treated with 100 ng/mL LPS,2 mmol/L metformin and 100 ng/mL LPS+2 mmol/L metformin to prepare conditioned medium.TE-1 cells were divided into 4 groups:Control group,LPS conditioned medium group (LPS group),metformin conditioned medium group (Met group) and LPS+metformin conditioned medium group (LPS+Met group).The migration ability of each group was observed by scratch test.Transwell chamber was used to detect cell invasion.Western blot was used to detect the expression of VEGF,Vimentin,E-cad and NEDD9.The concentrations of TNF-α and IL-8 were detected by ELISA.Results:Metformin significantly reduced the levels of MMP9,VEGF,TNF-α and IL-8 in TE-1 cells and macrophages in a dose-dependent manner compared with the control group (P＜0.05).Metformin significantly inhibited the migration and invasion of TE-1 cells (P＜0.05),significantly inhibit the expression of VEGF,Vimentin and NEDD9 (P＜0.05),and promote the expression of E-cad protein (P＜0.05).TNF-α and IL-8 levels in TE-1 cells were significantly decreased (P＜0.05).Conclusion:Metformin can reduce the expression of NEDD9 in esophageal carcinoma cells through macrophages,and inhibit the invasion and migration of esophageal carcinoma TE-1 cells. |
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| Keywords: | metformin esophageal cancer macrophages NEDD9 invasion migration |
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