半胱氨酰白三烯受体拮抗剂抑制人胶质母细胞瘤中 MMP-2/9 的迁移、侵袭和表达。
Cysteinyl Leukotriene Receptor Antagonists Inhibit Migration, Invasion, and Expression of MMP-2/9 in Human Glioblastoma.
机构信息
Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Department of Anatomy, Faculty of Science, Mahidol University, Bangkok, Thailand.
出版信息
Cell Mol Neurobiol. 2018 Mar;38(2):559-573. doi: 10.1007/s10571-017-0507-z. Epub 2017 Jun 9.
Abstract
Glioblastoma is one of the most malignant and aggressive types of brain tumors. 5-lipoxygenase and cysteinyl leukotriene receptor 1 (CysLT1) play a role in human carcinogenesis. Leukotriene receptor antagonists (LTRAs), anti-asthmatic drugs with mild side effects, have anti-metastatic activity in epidermoid carcinoma, lung carcinoma, and colon cancers as well as neuroprotective effects. Herein, anti-migratory effects of two LTRAs, montelukast and zafirlukast, were investigated in glioblastoma cells. The level of CysLT1 in A172 cells was increased by 3.13 folds after IL-1β treatment. The median toxic concentration of LTRAs in A172, U373, and primary astrocytes ranged from 7.17 to 26.28 μM at 24-h post-exposure. Both LTRAs inhibited migration and invasion of glioma. Additionally, both drugs significantly inhibited the expression and activities of MMP-2 and MMP-9 in A172 and U373 glioblastoma cells and primary human astrocytes, suggesting that CysLT1 plays a role in migration and invasion of glioma, and LTRAs are potential drugs to reduce migration and invasion.
摘要
胶质母细胞瘤是最恶性和侵袭性的脑肿瘤之一。5-脂氧合酶和半胱氨酰白三烯受体 1（CysLT1）在人类肿瘤发生中起作用。白三烯受体拮抗剂（LTRA）是一种副作用较小的抗哮喘药物，在表皮样癌、肺癌、结肠癌以及神经保护方面具有抗转移活性。在此，研究了两种 LTRA（孟鲁司特和扎鲁司特）对胶质母细胞瘤细胞的迁移抑制作用。IL-1β处理后 A172 细胞中的 CysLT1 水平增加了 3.13 倍。在暴露后 24 小时，LTRA 在 A172、U373 和原代星形胶质细胞中的半数毒性浓度范围为 7.17 至 26.28 μM。两种 LTRA 均抑制胶质瘤的迁移和侵袭。此外，两种药物均显著抑制 A172 和 U373 胶质母细胞瘤细胞以及原代人星形胶质细胞中 MMP-2 和 MMP-9 的表达和活性，表明 CysLT1 参与了胶质瘤的迁移和侵袭，LTRA 可能是减少迁移和侵袭的潜在药物。
相似文献
1
Cysteinyl Leukotriene Receptor Antagonists Inhibit Migration, Invasion, and Expression of MMP-2/9 in Human Glioblastoma.半胱氨酰白三烯受体拮抗剂抑制人胶质母细胞瘤中 MMP-2/9 的迁移、侵袭和表达。
Cell Mol Neurobiol. 2018 Mar;38(2):559-573. doi: 10.1007/s10571-017-0507-z. Epub 2017 Jun 9.
2
Cysteinyl leukotriene receptor antagonists induce apoptosis and inhibit proliferation of human glioblastoma cells by downregulating B-cell lymphoma 2 and inducing cell cycle arrest.半胱氨酰白三烯受体拮抗剂通过下调B细胞淋巴瘤2并诱导细胞周期停滞来诱导人胶质母细胞瘤细胞凋亡并抑制其增殖。
Can J Physiol Pharmacol. 2018 Aug;96(8):798-806. doi: 10.1139/cjpp-2017-0757. Epub 2018 May 4.
3
Concentration-dependent noncysteinyl leukotriene type 1 receptor-mediated inhibitory activity of leukotriene receptor antagonists.白三烯受体拮抗剂的浓度依赖性非半胱氨酰白三烯 1 型受体介导的抑制活性。
J Immunol. 2010 Feb 15;184(4):2219-25. doi: 10.4049/jimmunol.0900071. Epub 2010 Jan 18.
4
Cysteinyl leukotriene receptor type 1 antagonist montelukast protects against injury of blood-brain barrier.半胱氨酰白三烯受体 1 拮抗剂孟鲁司特钠可预防血脑屏障损伤。
Inflammopharmacology. 2019 Oct;27(5):933-940. doi: 10.1007/s10787-019-00611-7. Epub 2019 Jul 16.
5
Neuromodulatory effects of leukotriene receptor antagonists: A comprehensive review.白三烯受体拮抗剂的神经调节作用：全面综述。
Eur J Pharmacol. 2024 Sep 5;978:176755. doi: 10.1016/j.ejphar.2024.176755. Epub 2024 Jun 21.
6
Leukotriene Receptor Antagonists Inhibit Mitogenic Activity in Triple Negative Breast Cancer Cells.白三烯受体拮抗剂抑制三阴性乳腺癌细胞的促有丝分裂活性。
Asian Pac J Cancer Prev. 2018 Mar 27;19(3):833-837. doi: 10.22034/APJCP.2018.19.3.833.
7
Mechanisms underlying the protective effect of leukotriene receptor antagonist montelukast against doxorubicin induced testicular injury in rats.白三烯受体拮抗剂孟鲁司特对多柔比星诱导的大鼠睾丸损伤的保护作用机制。
Prostaglandins Other Lipid Mediat. 2020 Aug;149:106447. doi: 10.1016/j.prostaglandins.2020.106447. Epub 2020 Mar 12.
8
Anti-Migration and Invasion Effects of Astaxanthin against A172 Human Glioblastoma Cell Line.虾青素对 A172 人神经胶质瘤细胞系的抗迁移和侵袭作用。
Asian Pac J Cancer Prev. 2020 Jul 1;21(7):2029-2033. doi: 10.31557/APJCP.2020.21.7.2029.
9
PEITC inhibits human brain glioblastoma GBM 8401 cell migration and invasion through the inhibition of uPA, Rho A, and Ras with inhibition of MMP-2, -7 and -9 gene expression.苯乙基异硫氰酸酯（PEITC）通过抑制尿激酶型纤溶酶原激活剂（uPA）、Rho A和Ras，并抑制基质金属蛋白酶-2、-7和-9的基因表达，从而抑制人脑胶质母细胞瘤GBM 8401细胞的迁移和侵袭。
Oncol Rep. 2015 Nov;34(5):2489-96. doi: 10.3892/or.2015.4260. Epub 2015 Sep 8.
10
The leukotriene receptor antagonist montelukast and its possible role in the cardiovascular field.白三烯受体拮抗剂孟鲁司特及其在心血管领域的潜在作用。
Eur J Clin Pharmacol. 2017 Jul;73(7):799-809. doi: 10.1007/s00228-017-2242-2. Epub 2017 Apr 4.
引用本文的文献
1
Cysteine Leukotriene Receptor Antagonist-Montelukast-Treatment Improves Experimental Abdominal Aortic Aneurysms in Mice.半胱氨酰白三烯受体拮抗剂——孟鲁司特——治疗可改善小鼠实验性腹主动脉瘤
Cardiovasc Ther. 2024 Nov 27;2024:8826287. doi: 10.1155/2024/8826287. eCollection 2024.
2
Network pharmacology combined with experimental verification to explore the potential mechanism of naringenin in the treatment of cervical cancer.网络药理学结合实验验证探讨柚皮素治疗宫颈癌的潜在机制。
Sci Rep. 2024 Jan 22;14(1):1860. doi: 10.1038/s41598-024-52413-9.
3
Montelukast Inhibits Lung Cancer Cell Migration by Suppressing Cysteinyl Leukotriene Receptor 1 Expression .孟鲁司特通过抑制半胱氨酰白三烯受体 1 表达抑制肺癌细胞迁移。
Curr Pharm Biotechnol. 2023;24(10):1335-1342. doi: 10.2174/1389201024666221207143513.
4
Exploring the inverse association of glioblastoma multiforme and Alzheimer's disease via bioinformatics analysis.通过生物信息学分析探索胶质母细胞瘤和阿尔茨海默病的负相关关系。
Med Oncol. 2022 Sep 7;39(12):182. doi: 10.1007/s12032-022-01786-w.
5
Exploration of Potential Ewing Sarcoma Drugs from FDA-Approved Pharmaceuticals through Computational Drug Repositioning, Pharmacogenomics, Molecular Docking, and MD Simulation Studies.通过计算药物重新定位、药物基因组学、分子对接和分子动力学模拟研究，从美国食品药品监督管理局（FDA）批准的药物中探索潜在的尤因肉瘤药物。
ACS Omega. 2022 Jun 1;7(23):19243-19260. doi: 10.1021/acsomega.2c00518. eCollection 2022 Jun 14.
6
Effects of Montelukast on Arsenic-Induced Epithelial-Mesenchymal Transition and the Role of Reactive Oxygen Species Production in Human Bronchial Epithelial Cells.孟鲁司特对砷诱导的人支气管上皮细胞上皮-间质转化的影响及活性氧生成的作用
Front Pharmacol. 2022 Apr 19;13:877125. doi: 10.3389/fphar.2022.877125. eCollection 2022.
7
Juxtamembrane 2 mimic peptide competitively inhibits mitochondrial trafficking and activates ROS-mediated apoptosis pathway to exert anti-tumor effects.衔接膜 2 模拟肽竞争性抑制线粒体运输并激活 ROS 介导的凋亡途径发挥抗肿瘤作用。
Cell Death Dis. 2022 Mar 24;13(3):264. doi: 10.1038/s41419-022-04639-6.
8
Cysteinyl Leukotriene Pathway and Cancer.半胱氨酰白三烯途径与癌症。
Int J Mol Sci. 2021 Dec 23;23(1):120. doi: 10.3390/ijms23010120.
9
Zafirlukast is a broad-spectrum thiol isomerase inhibitor that inhibits thrombosis without altering bleeding times.扎鲁司特是一种广谱硫醇异构酶抑制剂，能抑制血栓形成而不改变出血时间。
Br J Pharmacol. 2021 Feb;178(3):550-563. doi: 10.1111/bph.15291. Epub 2021 Jan 4.
10
Inhibition of chromosomal region maintenance 1 suppresses the migration and invasion of glioma cells via inactivation of the STAT3/MMP2 signaling pathway.染色体区域维持蛋白1的抑制通过STAT3/MMP2信号通路失活抑制胶质瘤细胞的迁移和侵袭。
Korean J Physiol Pharmacol. 2020 May 1;24(3):193-201. doi: 10.4196/kjpp.2020.24.3.193.
本文引用的文献
1
Serum 5-LOX: a progressive protein marker for breast cancer and new approach for therapeutic target.血清5-脂氧合酶：一种用于乳腺癌的进展性蛋白质标志物及治疗靶点的新方法。
Carcinogenesis. 2016 Sep;37(9):912-7. doi: 10.1093/carcin/bgw075. Epub 2016 Jul 18.
2
Effects of montelukast on M2-related cytokine and chemokine in M2 macrophages.孟鲁司特对 M2 型巨噬细胞中 M2 相关细胞因子和趋化因子的影响。
J Microbiol Immunol Infect. 2018 Feb;51(1):18-26. doi: 10.1016/j.jmii.2016.04.005. Epub 2016 May 13.
3
Cysteinyl Leukotriene Receptor Antagonists Decrease Cancer Risk in Asthma Patients.半胱氨酰白三烯受体拮抗剂降低哮喘患者的癌症风险。
Sci Rep. 2016 Apr 7;6:23979. doi: 10.1038/srep23979.
4
Comparison of MMP2 and MMP9 expression levels between primary and metastatic regions of oral squamous cell carcinoma.口腔鳞状细胞癌原发灶与转移灶中MMP2和MMP9表达水平的比较。
J Oral Sci. 2016;58(1):59-65. doi: 10.2334/josnusd.58.59.
5
Role of cysteinyl leukotriene receptor-1 antagonists in treatment of experimentally induced mammary tumor: does montelukast modulate antitumor and immunosuppressant effects of doxorubicin?半胱氨酰白三烯受体-1拮抗剂在实验性诱导乳腺肿瘤治疗中的作用：孟鲁司特是否调节阿霉素的抗肿瘤和免疫抑制作用？
Toxicol Ind Health. 2015 Nov;31(11):1024-36. doi: 10.1177/0748233713485884. Epub 2013 Apr 19.
6
Elucidating the cancer-specific genetic alteration spectrum of glioblastoma derived cell lines from whole exome and RNA sequencing.通过全外显子组测序和RNA测序阐明胶质母细胞瘤衍生细胞系的癌症特异性基因改变谱。
Oncotarget. 2015 Dec 22;6(41):43452-71. doi: 10.18632/oncotarget.6171.
7
Naringin inhibits the invasion and migration of human glioblastoma cell via downregulation of MMP-2 and MMP-9 expression and inactivation of p38 signaling pathway.柚皮苷通过下调MMP-2和MMP-9的表达以及使p38信号通路失活来抑制人胶质母细胞瘤细胞的侵袭和迁移。
Tumour Biol. 2016 Mar;37(3):3831-9. doi: 10.1007/s13277-015-4230-4. Epub 2015 Oct 16.
8
Characterization of matrix metalloproteinase-2 and -9, ADAM-10 and N-cadherin expression in human glioblastoma multiforme.多形性胶质母细胞瘤中基质金属蛋白酶-2和-9、ADAM-10及N-钙黏蛋白表达的特征分析
Cell Tissue Res. 2015 Oct;362(1):45-60. doi: 10.1007/s00441-015-2197-5. Epub 2015 May 7.
9
Zileuton, 5-lipoxygenase inhibitor, acts as a chemopreventive agent in intestinal polyposis, by modulating polyp and systemic inflammation.齐留通，一种5-脂氧合酶抑制剂，通过调节息肉和全身炎症，在肠道息肉病中作为一种化学预防剂发挥作用。
PLoS One. 2015 Mar 6;10(3):e0121402. doi: 10.1371/journal.pone.0121402. eCollection 2015.
10
Histamine induces the production of matrix metalloproteinase-9 in human astrocytic cultures via H1-receptor subtype.组胺通过H1受体亚型在人星形胶质细胞培养物中诱导基质金属蛋白酶-9的产生。
Brain Struct Funct. 2016 May;221(4):1845-60. doi: 10.1007/s00429-015-1007-x. Epub 2015 Feb 15.
Zotero 插件