中国肿瘤生物治疗杂志2018，Vol.25Issue(2)：125-131,7.DOI:10.3872/j.issn.1007-385x.2018.02.003
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
摘要
Abstract
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 significantly higher than 60.0％ (9/15) in the control group (x2=7.500,P=0.006) and 73.3％ (11/15) in the hypoxia + Boc2 treatment group (x2=4.615,P=0.032).The expression of E-cad and MMP-9 protein in hypoxia group was significantly higher than that in control group (P＜0.01),while Boc2 treatment significantly decreased the expression of E-cad and MMP-9 protein in hypoxia group (P＜0.05).Conclusions:FPR1 antagonist Boc2 can significantly inhibit the migration,invasion,proliferation and tumorigenicity of hypoxia-induced human lung adenocarcinoma A549 cells,indicating that FPR1 plays an important role in the development and progression of human lung adenocarcinoma and may become a potential target of human lung adenocarcinoma treatment.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Key words
lung adenocarcinoma/A549 cell/hypoxia/formyl peptide receptor 1 (FPR1)/migration/invasion/proliferation/tumorigenicity分类
医药卫生引用本文复制引用
黄波,丁洁,郭红荣..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[J].中国肿瘤生物治疗杂志,2018,25(2):125-131,7.基金项目
武汉市卫生计生委科研基金(No.WX16D11).Project supported by the Science Foundation of Health and Family Planning Commission of Wuhan Municipality (No.WX16D11) （No.WX16D11）
