预防医学2024,Vol.36Issue(3) :272-276.DOI:10.19485/j.cnki.issn2096-5087.2024.03.022

十溴联苯醚对小鼠宫颈癌皮下移植瘤相关基因及信号通路的影响

Effects of decabromodiphenyl ether on genes and signaling pathways related to subcutaneous transplanted tumors of cervical cancer in mice

祖尼热·吐尔逊 陈楠 马英杰 阿尔娜·恰依马尔旦 张雪寒 刘早玲
预防医学2024,Vol.36Issue(3) :272-276.DOI:10.19485/j.cnki.issn2096-5087.2024.03.022

十溴联苯醚对小鼠宫颈癌皮下移植瘤相关基因及信号通路的影响

Effects of decabromodiphenyl ether on genes and signaling pathways related to subcutaneous transplanted tumors of cervical cancer in mice

祖尼热·吐尔逊 1陈楠 1马英杰 1阿尔娜·恰依马尔旦 1张雪寒 1刘早玲1
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作者信息

  • 1. 新疆医科大学公共卫生学院,新疆 乌鲁木齐 830011
  • 折叠

摘要

目的 探讨十溴联苯醚(BDE-209)对小鼠宫颈癌皮下移植瘤大小、相关基因及信号通路的影响.方法 40只雌性C57BL/6小鼠腋窝外侧皮下接种小鼠宫颈癌U14细胞,建立小鼠宫颈癌皮下移植瘤模型,随机分为高剂量组(500 mg/kg)、中剂量组(100 mg/kg)、低剂量组(20 mg/kg)和对照组(玉米油),采用灌胃方式给予相应剂量的BDE-209或玉米油.21 d后取皮下移植瘤组织,采用高通量转录组测序技术分析皮下移植瘤的差异表达基因,并进行基因本体论(GO)功能注释和京都基因与基因组百科全书(KEGG)富集分析;采用STRING数据库进行蛋白相互作用分析,并筛选关键基因;采用实时荧光定量PCR法测定关键基因mRNA的表达.结果 与对照组、低剂量组、中剂量组相比,BDE-209高剂量组小鼠宫颈癌皮下移植瘤质量下降(均P<0.05).转录组测序结果显示,与对照组相比,高剂量组2 011个基因表达上调,1 165个基因表达下调;中剂量组960个基因表达上调,357个基因表达下调;低剂量组537个基因表达上调,262个基因表达下调(均P<0.05);GO和KEGG富集分析结果显示,高剂量组的差异表达基因主要富集于细胞趋化、NOD样受体信号通路等;中剂量组差异表达基因主要富集于细胞趋化、细胞因子-细胞因子受体的相互作用等;低剂量组差异表达基因主要富集于抗原的处理和呈递、补体和凝血级联信号通路等.与对照组相比,高剂量组TLR2、MMP9、IL-6、Fos和TNF的mRNA表达上调(均P<0.05).结论 高剂量BDE-209可能影响Toll样受体、NOD样受体等免疫及炎症相关信号通路及基因,使小鼠宫颈癌皮下移植瘤质量下降.

Abstract

Objective To investigate the effects of decabromodiphenyl ether(BDE-209)on the size of subcutaneous transplanted tumors,related genes and signaling pathways of cervical cancer in mice.Methods Forty female C57BL/6 mice were subcutaneously inoculated with mouse cervical carcinoma U14 cells in the lateral axilla to establish a mouse subcutaneous transplanted tumor model.These mice were randomly divided into a high-dose group(500 mg/kg),a medi-um-dose group(100 mg/kg),a low-dose group(20 mg/kg)and a control group(corn oil),and were exposed to BDE-209 or corn oil by gavage.Subcutaneous transplanted tumor tissue was taken after 21 days of BDE-209 poisoning,and the differentially expressed genes in the subcutaneous transplanted tumors of cervical cancer among the four groups were analyzed by high-throughput transcriptome sequencing and were subjected to Gene Ontology(GO)annotations and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Protein-protein interactions(PPI)were analyzed using the STRING database,and the mRNA expression of hub genes was determined by real-time fluorescence poly-merase chain reaction.Results Compared with the control group,low-dose group and medium-dose group,the mass of subcutaneous transplanted tumors in the high-dose group was decreased(all P<0.05).Transcriptome sequencing results showed that compared with the control group,2 011 genes were up-regulated and 1 165 genes were down-regulated in the high-dose group;960 genes were up-regulated and 357 genes were down-regulated in the medium-dose group;537 genes were up-regulated and 262 genes were down-regulated in the low-dose group(all P<0.05).GO and KEGG analy-sis showed that the differentially expressed genes in the high-dose group were mainly involved in cell chemotaxis and NOD-like receptor signaling pathway;the differentially expressed genes in the medium-dose group were mainly involved in cell chemotaxis and cytokine-cytokine receptor interactions;and the differentially expressed genes in the medium-dose group were mainly involved in processing and presentation of antigens,and the signaling pathways of the comple-ment and coagulation cascades.Compared with the control group,the mRNA expression of TLR2,MMP9,IL-6,Fos,and TNF was up-regulated in the high-dose group(all P<0.05).Conclusion High-dose BDE-209 may affect Toll-like receptors,NOD-like receptors,and other immune and inflammatory-related signaling pathways and cancer-related genes,leading to a decrease in the mass of subcutaneous transplanted cervical cancer tumors in mice.

关键词

十溴联苯醚/宫颈癌/皮下移植瘤/信号通路/关键基因

Key words

decabromodiphenyl ether/cervical cancer/subcutaneous transplantation tumor/signaling pathway/hub gene

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基金项目

省部共建中亚高发病成因与防治国家重点实验室资助项目(SKL-HIDCA-2020-ER2)

国家级大学生创新训练计划项目(202210760014)

出版年

2024
预防医学
浙江省预防医学会

预防医学

CSTPCD
影响因子:1.002
ISSN:2096-5087
参考文献量17
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