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 medium-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 polymerase 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 analysis 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 complement 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.
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. 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[J]. 预防医学, 2024, 36(3): 272-276.
Zunire Tuerxun, CHEN Nan, MA Yingjie, Aerna Qiayimaerdan, ZHANG Xuehan, LIU Zaoling. Effects of decabromodiphenyl ether on genes and signaling pathways related to subcutaneous transplanted tumors of cervical cancer in mice. Preventive Medicine, 2024, 36(3): 272-276.
[1] COHEN P A,JHINGRAN A,OAKIN A,et al.Cervical cancer[J].Lancet,2019,393(10167):169-182. [2] BREHM E,FLAWS J A.Transgenerational effects of endocrine-disrupting chemicals on male and female reproduction[J].Endocrinology,2019,160(6):1421-1435. [3] KORSAKOV A V,KRYUKOVA A E,TROSHIN V P,et al.Cervical and endometrial cancer incidence in the female population from the Bryansk Region living in conditions of chemical,radioactive and combined environmental contamination(2000-2020)[J].Life(Basel),2022,12(10):1-19. [4] YUAN J W,SUN X M,CHE S Y,et al.AhR-mediated CYP1A1 and ROS overexpression are involved in hepatotoxicity of decabromodiphenyl ether(BDE-209)[J/OL].Toxicol Lett,2021[2024-02-22].https://doi.org/10.1016/j.toxlet.2021.09.008. [5] DEZIEL N C,ALFONSO-GARRIDO J,WARREN J L,et al.Exposure to polybrominated diphenyl ethers and a polybrominated biphenyl and risk of thyroid cancer in women:single and multi-pollutant approaches[J].Cancer Epidemiol Biomarkers Prev,2019,28(10):1755-1764. [6] LI Z H,LIU X Y,WANG N,et al.Effects of decabrominated diphenyl ether(PBDE-209)in regulation of growth and apoptosis of breast,ovarian,and cervical cancer cells[J].Environ Health Perspect,2012,120(4):541-546. [7] LIM J S,LEE D H,JACOBS D R Jr.Association of brominated flame retardants with diabetes and metabolic syndrome in the U.S.population,2003-2004[J].Diabetes Care,2008,31(9):1802-1807. [8] 王永治,李美艳,阿依古丽·阿力木,等.限制性立方样条分析乌鲁木齐市孕产妇多溴联苯醚暴露水平与新生儿低出生体重的剂量-反应关系[J].卫生研究,2019,48(3):440-445. [9] RENZELLI V,GALLO M,MORVIDUCCI L,et al.Polybrominated diphenyl ethers(pbdes)and human health:effects on metabolism,diabetes and cancer[J].Cancers(Basel),2023,15(17):1-19. [10] LIU P,LU Z W,LIU L L,et al.NOD-like receptor signaling in inflammation-associated cancers:from functions to targeted therapies[J/OL].Phytomedicine,2019,64[2024-02-22].https://doi.org/10.1016/j.phymed.2019.152925. [11] 林巧卫,张思,陆维祺.NOD样受体介导的信号转导通路及其与肿瘤关系的研究进展[J].中国癌症杂志,2019,29(3):223-228. [12] KESHAVARZ A,POURBAGHERI-SIGAROODI A,ZAFARI P,et al.Toll-like receptors(TLRs)in cancer;with an extensive focus on TLR agonists and antagonists[J].IUBMB Life,2021,73(1):10-25. [13] LIANG W Q,HE Y J,HE W G,et al.Exhausted CD8+T cells in the tumor immune microenvironment:new pathways to therapy[J/OL].Front Immunol,2021[2024-02-22].https://doi.org/10.3389/fimmu.2020.622509. [14] POH A R,O'DONOGHUE R J,ERNST M.Hematopoietic cell kinase(HCK)as a therapeutic target in immune and cancer cells[J].Oncotarget,2015,6(18):15752-15771. [15] 钟要红,何青芳,李迎君,等.基于GEO芯片数据库的结肠癌易感基因挖掘[J].预防医学,2017,29(11):1094-1097. [16] 蒋亚男,王薇,吴逢霞.宫颈癌患者血清及组织VEGF及MMP的变化[J].海南医学院学报,2015,21(4):556-558. [17] 张玉芳,任春丽,梁爽,等.宫颈鳞癌组织中c-fos蛋白表达与HPV感染的相关性[J].中国现代医学杂志,2018,28(34):23-26.
