低氧环境下甲酰肽受体1拮抗剂Boc2对人肺腺癌细胞恶性生物学行为的影响  

Effects of formyl peptide receptor 1 antagonist Boc2 on malignant biological behaviors of human lung adenocarcinoma cells under hypoxia conditions

作　　者：黄波[1] 丁洁[2] 郭红荣 

机构地区：[1]武汉大学附属同仁医院(武汉市第三医院)呼吸科,湖北武汉430070 [2]武汉大学附属同仁医院(武汉市第三医院)消化内科,湖北武汉430070

出　　处：《中国肿瘤生物治疗杂志》2018年第2期125-131,共7页Chinese Journal of Cancer Biotherapy

基　　金：武汉市卫生计生委科研基金(No.WX16D11)~~

摘　　要：目的:探讨低氧环境下甲酰肽受体1(formyl peptide receptor 1,FPR1)的拮抗剂Boc2对人肺腺癌细胞迁移、侵袭、增殖及成瘤能力的影响。方法:采用Western blotting检测低氧诱导下人肺腺癌细胞A549中低氧诱导因子1α(hypoxia inducible factor 1α,HIF-1α)和FPR1蛋白的表达情况。以FPR1拮抗剂Boc2体外处理低氧诱导的A549细胞,按照随机数字表法分为3组:对照组(常氧条件下培养)、低氧组和低氧+Boc2处理组。细胞划痕实验、Transwell细胞侵袭实验及MTT法分别用于检测各组细胞的迁移、侵袭和增殖能力。接种A549细胞制备裸鼠移植瘤模型,同上分3组,4周后处死裸鼠,分析各组间裸鼠移植瘤体积、质量、成瘤率以及迁移相关蛋白E-钙黏素(E-cadherin,E-cad)和侵袭相关蛋白MMP-9表达量的差异性。结果:低氧诱导能促进A549细胞FPR1蛋白的表达,且呈时间依赖性(P<0.05)。与对照组相比,低氧组细胞的迁移、侵袭及增殖能力均显著增强(P<0.01),而相对低氧组,Boc2处理能显著抑制A549细胞的迁移、侵袭和增殖能力(P<0.05)。低氧组裸鼠成瘤率为100.0%(15/15),对照组为60.0%(9/15),低氧+Boc2处理组裸鼠成瘤率为73.3%(11/15);低氧组裸鼠移植瘤体积、质量均显著高于对照组(均P<0.01);而相对低氧组,低氧+Boc2处理组裸鼠肿瘤体积、质量均有显著降低(均P<0.01)。低氧组E-cad及MMP-9蛋白表达量显著高于对照组(P<0.01),而与低氧组相比Boc2处理能显著降低E-cad及MMP-9蛋白表达量(P<0.05)。结论:FPR1拮抗剂Boc2能显著抑制低氧诱导的人肺腺癌细胞A549的迁移、侵袭、增殖及成瘤能力,表明FPR1在人肺腺癌的发生发展过程中扮演着重要角色,并有可能成为人肺腺癌治疗的潜在靶点。Objective： To investigate the effects of FPR1（formyl peptide receptor 1） antagonist Boc2 on migration, invasion, proliferation and tumorigenicity of human lung adenocarcinoma cells under hypoxia conditions. Methods： The protein expressions of hypoxia inducible factor 1α（HIF-1α） and FPR1 in human lung adenocarcinoma A549 cells induced by hypoxia was detected by Western blotting. FPR1 antagonist Boc2 was used to treat the hypoxia-induced A549 cells in vitro. The cells were divided into three groups： control group（cultured under normoxic condition）, hypoxia group and hypoxia＋Boc2 treatment group. Cell scratch test, transwell matrigel invasion assay and MTT method were used to detect the migration, invasion and proliferation of each group of cells, respectively. The A549 cells of each group were inoculated into nude mice to prepare xenograft model. After 4 weeks, the nude mice were sacrificed, and the differences in average tumor volume and mass, tumor formation rate, the expression of migration-related protein-E-cadherin（E-cad）and invasion-related protein-matrix metalloproteinase 9（MMP-9） were analyzed. Results： Hypoxia induction can promote the expression of FPR1 protein in A549 cells in a time-dependent manner（P〈0.05）. The results of cell experiments showed that the ability of migration, invasion and proliferation of cells in hypoxia group were significantly higher than those in control group（P〈0.01）; while compared with hypoxia group, Boc2 treatment significantly inhibited the migration, invasion and proliferation of A549 cells（P〈0.05）. The results of nude mice experiments showed that the average volume and mass of nude mice in hypoxia group were significantly higher than those in the control group（all P〈0.01）. But the mean volume and mass of nude mice in hypoxia＋Boc2 treatment group were significantly lower than those in the hypoxia group（all P〈0.01）. The rate of tumor formation in nude mice of hypoxia group was 100.0%（15/15）, which was signific

关 键 词：肺腺癌 A549细胞 低氧 甲酰肽受体1 迁移 侵袭 增殖 成瘤 

分 类 号：R734.2[医药卫生—肿瘤] R730.5[医药卫生—临床医学]