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2011个基因表达上调,1165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。
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,2011 genes were up-regulated and 1165 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
作者
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
Zunire Tuerxun;CHEN Nan;MA Yingjie;Aerna Qiayimaerdan;ZHANG Xuehan;LIU Zaoling(School of Public Health,Xinjiang Medical University,Urumqi,Xinjiang 830011,China)
出处
《预防医学》
2024年第3期272-276,共5页
CHINA PREVENTIVE MEDICINE JOURNAL
基金
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)。
关键词
十溴联苯醚
宫颈癌
皮下移植瘤
信号通路
关键基因
decabromodiphenyl ether
cervical cancer
subcutaneous transplantation tumor
signaling pathway
hub gene
