高级搜索

TCDD对胶质母细胞瘤中环氧合酶2基因表达的影响和生物学作用

,  ,  ,  ,  ,  , 

downloadPDF

上一篇

下一篇

彭颖蓓, 陈旸升, 刘奕耘, 李云平, 徐丽, 谢群慧, 赵斌. TCDD对胶质母细胞瘤中环氧合酶2基因表达的影响和生物学作用[J]. 生态毒理学报, 2023, 18(4): 241-252. doi: 10.7524/AJE.1673-5897.20230410003
引用本文: 彭颖蓓, 陈旸升, 刘奕耘, 李云平, 徐丽, 谢群慧, 赵斌. TCDD对胶质母细胞瘤中环氧合酶2基因表达的影响和生物学作用[J]. 生态毒理学报, 2023, 18(4): 241-252. doi: 10.7524/AJE.1673-5897.20230410003
shu
Peng Yingbei, Chen Yangsheng, Liu Yiyun, Li Yunping, Xu Li, Xie Qunhui, Zhao Bin. Effect of TCDD on Expression of Cyclooxygenase-2 Gene and Its Biological Role in Glioblastoma[J]. Asian journal of ecotoxicology, 2023, 18(4): 241-252. doi: 10.7524/AJE.1673-5897.20230410003
Citation: Peng Yingbei, Chen Yangsheng, Liu Yiyun, Li Yunping, Xu Li, Xie Qunhui, Zhao Bin. Effect of TCDD on Expression of Cyclooxygenase-2 Gene and Its Biological Role in Glioblastoma[J]. Asian journal of ecotoxicology, 2023, 18(4): 241-252. doi: 10.7524/AJE.1673-5897.20230410003
shu

TCDD对胶质母细胞瘤中环氧合酶2基因表达的影响和生物学作用

  • 1. 中国科学院生态环境研究中心, 环境化学与生态毒理学国家重点实验室, 北京 100085;

  • 2. 中国科学院大学资源与环境学院, 北京 100049;

  • 3. 重庆医科大学公共卫生学院, 重庆 400030;

  • 4. 国科大杭州高等研究院环境学院, 杭州 310024

    • 作者简介: 彭颖蓓(1998-),女,硕士研究生,研究方向为环境毒理学,E-mail:ybpeng_st@rcees.ac.cn
    通讯作者: 陈旸升,E-mail:yschen@rcees.ac.cn; 
  • 基金项目:

    国家自然科学基金青年项目(22206202)；国家自然科学基金重点项目(21836004)；国家重点研发计划项目(2018YFA0901100)

  • 中图分类号: X171.5

Effect of TCDD on Expression of Cyclooxygenase-2 Gene and Its Biological Role in Glioblastoma

  • 1. State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China;

  • 2. College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China;

  • 3. College of Public Health, Chongqing Medical University, Chongqing 400030, China;

  • 4. School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China

    • Corresponding author: Chen Yangsheng, yschen@rcees.ac.cn ; 
  • Fund Project:

  • 摘要: 胶质母细胞瘤(glioblastoma, GBM)是最常见的恶性脑肿瘤,其复发率和死亡率居高不下。环氧合酶2(cyclooxygenase 2, COX2)在正常生理条件下几乎不表达,但持续高表达的COX2常见于各种恶性肿瘤和癌前状态,并参与诸多肿瘤发生发展过程,如血管生成、免疫抑制、迁移侵袭以及化疗抵抗等。二噁英类污染物作为一级致癌物,但目前有关二噁英对GBM发展的研究十分有限。本研究旨在探究二噁英暴露影响GBM发展的分子机制。以COX2为标志物,明确二噁英类污染物中毒性最强的2,3,7,8-二苯并-p-二噁英(2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD)对胶质母细胞瘤U87细胞中COX2基因表达的影响以及芳香烃受体(aryl hydrocarbon receptor, AhR)在之中的作用,并借助转录组测序进一步探究TCDD暴露后U87细胞中COX2参与的生物过程。实验结果显示,TCDD以AhR依赖的方式上调U87细胞中COX2基因表达并具有时间-剂量依赖效应。转录组分析结果表明,TCDD暴露显著改变了U87细胞中细胞黏附、胞外刺激检测以及膜转运等相关通路的基因表达,COX2可能通过影响脂质形成和维持炎症反应参与U87的改变。进一步的互作分析发现COX2基因与IL1B和CYP2E1相关。本研究补充了TCDD在U87细胞中上调COX2表达的可能机制和影响,并为今后对二噁英促癌作用的研究提供参考。
    Abstract: Glioblastoma (GBM) is the most common malignant brain tumor which has high recurrence and mortality rate. Cyclooxygenase 2 (COX2) is not expressed under normal physiological conditions, but the continuously high expression of COX2 is common in various malignant tumors and precancerous states. COX2 is involved in many tumors' physiological activities, such as angiogenesis, immunosuppression, migration invasion, and chemotherapy resistance. As primary carcinogen, the research about dioxin on glioblastoma occurrence and development is very limited. This study is aimed to investigate the effect and mechanism of dioxin on the expression of COX2 gene and its subsequent effects on glioblastoma. We investigated the effect of dioxin on COX2 gene expression in glioblastoma U87 cells and the role of aryl hydrocarbon receptor (AhR). Through in vitro cell experiments, the most toxic dioxin, 2,3,7,8-dibenzo-p-dioxin (TCDD), was used as a representative pollutant to explore whether dioxin can change the expression of COX2 gene through the classical AhR pathway in U87 cell. Finally, transcriptome sequencing was used to further explore the biological role of COX2 in U87 cells after TCDD treatment. The experimental results showed that TCDD could upregulate the expression of COX2 gene in U87 cells in an AhR-dependent manner and had significant time-dependent and dose-dependent effects. The results of transcriptome analysis showed that TCDD exposure significantly altered cell adhesion, extracellular stimulation detection, and membrane transport pathways in U87 cells, and COX2 perhaps participate in the change of U87 by affecting lipid formation and maintaining inflammatory response. Through further interaction analysis, we found that COX2 gene was associated with IL1B and CYP2E1. This study supplements the possible mechanism and influence of TCDD upregulating COX2 expression in U87 cells, and provides more details for future researches on the cancer promoting effect of dioxins.
  • 加载中
  • Rodríguez-Camacho A, Flores-Vázquez J G, Moscardini-Martelli J, et al. Glioblastoma treatment:State-of-the-art and future perspectives[J]. International Journal of Molecular Sciences, 2022, 23(13):7207
    Zhai L J, Lauing K L, Chang A L, et al. The role of IDO in brain tumor immunotherapy[J]. Journal of Neuro-Oncology, 2015, 123(3):395-403
    Ladomersky E, Scholtens D M, Kocherginsky M, et al. The coincidence between increasing age, immunosuppression, and the incidence of patients with glioblastoma[J]. Frontiers in Pharmacology, 2019, 10:200
    Rios A, Vargas-Robles H, Gámez-Méndez A M, et al. Cyclooxygenase-2 and kidney failure[J]. Prostaglandins & Other Lipid Mediators, 2012, 98(3-4):86-90
    Cook P J, Thomas R, Kingsley P J, et al. Cox-2-derived PGE2 induces Id1-dependent radiation resistance and self-renewal in experimental glioblastoma[J]. Neuro-Oncology, 2016, 18(10):1379-1389
    Lyons T R, O'Brien J, Borges V F, et al. Postpartum mammary gland involution drives progression of ductal carcinoma in situ through collagen and COX-2[J]. Nature Medicine, 2011, 17(9):1109-1115
    Manchana T, Triratanachat S, Sirisabya N, et al. Prevalence and prognostic significance of COX-2 expression in stage IB cervical cancer[J]. Gynecologic Oncology, 2006, 100(3):556-560
    Gasparini G, Longo R, Sarmiento R, et al. Inhibitors of cyclo-oxygenase 2:A new class of anticancer agents?[J]. The Lancet Oncology, 2003, 4(10):605-615
    Alique M, Calleros L, Luengo A, et al. Changes in extracellular matrix composition regulate cyclooxygenase-2 expression in human mesangial cells[J]. American Journal of Physiology Cell Physiology, 2011, 300(4):C907-C918
    Privorotskiy A, Bhavsar S P, Lang F F, et al. Impact of anesthesia and analgesia techniques on glioblastoma progression. A narrative review[J]. Neuro-Oncology Advances, 2020, 2(1):vdaa123
    Fernandez-Salguero P M, Hilbert D M, Rudikoff S, et al. Aryl-hydrocarbon receptor-deficient mice are resistant to 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced toxicity[J]. Toxicology and Applied Pharmacology, 1996, 140(1):173-179
    Shivanna B, Chu C, Moorthy B. The aryl hydrocarbon receptor (AHR):A novel therapeutic target for pulmonary diseases?[J]. International Journal of Molecular Sciences, 2022, 23(3):1516
    Ochs K, Ott M, Rauschenbach K J, et al. Tryptophan-2,3-dioxygenase is regulated by prostaglandin E2 in malignant glioma via a positive signaling loop involving prostaglandin E receptor-4[J]. Journal of Neurochemistry, 2016, 136(6):1142-1154
    Zhu P Y, Yu H Y, Zhou K, et al. 3,3'-diindolylmethane modulates aryl hydrocarbon receptor of esophageal squamous cell carcinoma to reverse epithelial-mesenchymal transition through repressing RhoA/ROCK1-mediated COX2/PGE2 pathway[J]. Journal of Experimental & Clinical Cancer Research, 2020, 39(1):113
    Hanieh H, Ibrahim H M, Mohammed M, et al. Activation of aryl hydrocarbon receptor signaling by gallic acid suppresses progression of human breast cancer in vitro and in vivo[J]. Phytomedicine:International Journal of Phytotherapy and Phytopharmacology, 2022, 96:153817
    Enan E, El-Sabeawy F, Scott M, et al. Alterations in the growth factor signal transduction pathways and modulators of the cell cycle in endocervical cells from macaques exposed to TCDD[J]. Toxicology and Applied Pharmacology, 1998, 151(2):283-293
    Warner M, Mocarelli P, Samuels S, et al. Dioxin exposure and cancer risk in the Seveso Women's Health Study[J]. Environmental Health Perspectives, 2011, 119(12):1700-1705
    Bui L C, Tomkiewicz C, Pierre S, et al. Regulation of aquaporin 3 expression by the AhR pathway is critical to cell migration[J]. Toxicological Sciences:An Official Journal of the Society of Toxicology, 2016, 149(1):158-166
    Liu Y Y, Chen Y S, Sha R, et al. A new insight into the role of aryl hydrocarbon receptor (AhR) in the migration of glioblastoma by AhR-IL24 axis regulation[J]. Environment International, 2021, 154:106658
    Lee W, Park S, Kang S K, et al. Cancer risk in Vietnam war veterans from the Korean Vietnam war veterans' health study cohort[J]. Frontiers in Oncology, 2023, 13:1048820
    Schug T T, Janesick A, Blumberg B, et al. Endocrine disrupting chemicals and disease susceptibility[J]. The Journal of Steroid Biochemistry and Molecular Biology, 2011, 127(3-5):204-215
    Mesnil M, Defamie N, Naus C, et al. Brain disorders and chemical pollutants:A gap junction link?[J]. Biomolecules, 2020, 11(1):51
    Juricek L, Coumoul X. The aryl hydrocarbon receptor and the nervous system[J]. International Journal of Molecular Sciences, 2018, 19(9):2504
    Gabriely G, Wheeler M A, Takenaka M C, et al. Role of AHR and HIF-1α in glioblastoma metabolism[J]. Trends in Endocrinology and Metabolism, 2017, 28(6):428-436
    Opitz C A, Litzenburger U M, Sahm F, et al. An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor[J]. Nature, 2011, 478(7368):197-203
    Wölfle D, Marotzki S, Dartsch D, et al. Induction of cyclooxygenase expression and enhancement of malignant cell transformation by 2,3,7,8-tetrachlorodibenzo-p-dioxin[J]. Carcinogenesis, 2000, 21(1):15-21
    Li Y, Wang K, Zou Q Y, et al. A possible role of aryl hydrocarbon receptor in spontaneous preterm birth[J]. Medical Hypotheses, 2015, 84(5):494-497
    Casado F L, Singh K P, Gasiewicz T A. Aryl hydrocarbon receptor activation in hematopoietic stem/progenitor cells alters cell function and pathway-specific gene modulation reflecting changes in cellular trafficking and migration[J]. Molecular Pharmacology, 2011, 80(4):673-682
    Ho I C, Lee T C. Arsenite pretreatment attenuates benzo[a]pyrene cytotoxicity in a human lung adenocarcinoma cell line by decreasing cyclooxygenase-2 levels[J]. Journal of Toxicology and Environmental Health Part A, 2002, 65(3-4):245-263
    Rebe C, Ghiringhelli F. Interleukin-1beta and cancer[J]. Cancers (Basel), 2020, 12(7):1-31
    Anzenbacher P, Anzenbacherová E. Cytochromes P450 and metabolism of xenobiotics[J]. Cellular and Molecular Life Sciences, 2001, 58(5):737-747
    Pollenz R S. The mechanism of AH receptor protein down-regulation (degradation) and its impact on AH receptor-mediated gene regulation[J]. Chemico-Biological Interactions, 2002, 141(1-2):41-61
    Lim T X, Ahamed M, Reutens D C. The aryl hydrocarbon receptor:A diagnostic and therapeutic target in glioma[J]. Drug Discovery Today, 2022, 27(2):422-435
    Ye Y, Wang X P, Jeschke U, et al. COX-2-PGE2-EPs in gynecological cancers[J]. Archives of Gynecology and Obstetrics, 2020, 301(6):1365-1375
    Eberstål S, Badn W, Fritzell S, et al. Inhibition of cyclooxygenase-2 enhances immunotherapy against experimental brain tumors[J]. Cancer Immunology, Immunotherapy, 2012, 61(8):1191-1199
    Basudhar D, Bharadwaj G, Somasundaram V, et al. Understanding the tumour micro-environment communication network from an NOS2/COX2 perspective[J]. British Journal of Pharmacology, 2019, 176(2):155-176
    Kang K B, Zhu C J, Yong S K, et al. Enhanced sensitivity of celecoxib in human glioblastoma cells:Induction of DNA damage leading to p53-dependent G1 cell cycle arrest and autophagy[J]. Molecular Cancer, 2009, 8:66
    Tu S P, Bhagat G, Cui G L, et al. Overexpression of interleukin-1beta induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice[J]. Cancer Cell, 2008, 14(5):408-419
    Trafalis D T, Panteli E S, Grivas A, et al. CYP2E1 and risk of chemically mediated cancers[J]. Expert Opinion on Drug Metabolism & Toxicology, 2010, 6(3):307-319
  • 加载中
WeChat 点击查看大图
计量
  • 文章访问数:  1275
  • HTML全文浏览数:  1275
  • PDF下载数:  107
  • 施引文献:  0
出版历程
  • 收稿日期:  2023-04-10
彭颖蓓, 陈旸升, 刘奕耘, 李云平, 徐丽, 谢群慧, 赵斌. TCDD对胶质母细胞瘤中环氧合酶2基因表达的影响和生物学作用[J]. 生态毒理学报, 2023, 18(4): 241-252. doi: 10.7524/AJE.1673-5897.20230410003
引用本文: 彭颖蓓, 陈旸升, 刘奕耘, 李云平, 徐丽, 谢群慧, 赵斌. TCDD对胶质母细胞瘤中环氧合酶2基因表达的影响和生物学作用[J]. 生态毒理学报, 2023, 18(4): 241-252. doi: 10.7524/AJE.1673-5897.20230410003
shu
Peng Yingbei, Chen Yangsheng, Liu Yiyun, Li Yunping, Xu Li, Xie Qunhui, Zhao Bin. Effect of TCDD on Expression of Cyclooxygenase-2 Gene and Its Biological Role in Glioblastoma[J]. Asian journal of ecotoxicology, 2023, 18(4): 241-252. doi: 10.7524/AJE.1673-5897.20230410003
Citation: Peng Yingbei, Chen Yangsheng, Liu Yiyun, Li Yunping, Xu Li, Xie Qunhui, Zhao Bin. Effect of TCDD on Expression of Cyclooxygenase-2 Gene and Its Biological Role in Glioblastoma[J]. Asian journal of ecotoxicology, 2023, 18(4): 241-252. doi: 10.7524/AJE.1673-5897.20230410003
shu

TCDD对胶质母细胞瘤中环氧合酶2基因表达的影响和生物学作用

    通讯作者: 陈旸升,E-mail:yschen@rcees.ac.cn; 
    作者简介: 彭颖蓓(1998-),女,硕士研究生,研究方向为环境毒理学,E-mail:ybpeng_st@rcees.ac.cn
  • 1. 中国科学院生态环境研究中心, 环境化学与生态毒理学国家重点实验室, 北京 100085;
  • 2. 中国科学院大学资源与环境学院, 北京 100049;
  • 3. 重庆医科大学公共卫生学院, 重庆 400030;
  • 4. 国科大杭州高等研究院环境学院, 杭州 310024
  • 收稿日期:  2023-04-10
基金项目:

国家自然科学基金青年项目(22206202)；国家自然科学基金重点项目(21836004)；国家重点研发计划项目(2018YFA0901100)

摘要: 胶质母细胞瘤(glioblastoma, GBM)是最常见的恶性脑肿瘤,其复发率和死亡率居高不下。环氧合酶2(cyclooxygenase 2, COX2)在正常生理条件下几乎不表达,但持续高表达的COX2常见于各种恶性肿瘤和癌前状态,并参与诸多肿瘤发生发展过程,如血管生成、免疫抑制、迁移侵袭以及化疗抵抗等。二噁英类污染物作为一级致癌物,但目前有关二噁英对GBM发展的研究十分有限。本研究旨在探究二噁英暴露影响GBM发展的分子机制。以COX2为标志物,明确二噁英类污染物中毒性最强的2,3,7,8-二苯并-p-二噁英(2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD)对胶质母细胞瘤U87细胞中COX2基因表达的影响以及芳香烃受体(aryl hydrocarbon receptor, AhR)在之中的作用,并借助转录组测序进一步探究TCDD暴露后U87细胞中COX2参与的生物过程。实验结果显示,TCDD以AhR依赖的方式上调U87细胞中COX2基因表达并具有时间-剂量依赖效应。转录组分析结果表明,TCDD暴露显著改变了U87细胞中细胞黏附、胞外刺激检测以及膜转运等相关通路的基因表达,COX2可能通过影响脂质形成和维持炎症反应参与U87的改变。进一步的互作分析发现COX2基因与IL1B和CYP2E1相关。本研究补充了TCDD在U87细胞中上调COX2表达的可能机制和影响,并为今后对二噁英促癌作用的研究提供参考。

English Abstract

参考文献 (39)

返回顶部

目录

/

返回文章
返回

Copyright © 2019 中国科学院生态环境研究中心

京ICP备05002858号-9