• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

抑制LRRK2可通过调节TLR4/NF-κB通路和NLRP3炎性小体来抑制肺癌进展。

Knockdown of LRRK2 inhibits the progression of lung cancer by regulating TLR4/NF-κB pathways and NLRP3 inflammasome.

作者信息

Wu Junfang, Yang Shumei, Wu Hua, Huang Yongcheng, Miao Yi

机构信息

Department of Respiratory Medicine, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, China.

Department of Pathology, Xi'an Central Hospital, Xi'an, Shaanxi 710004, China.

出版信息

J Clin Biochem Nutr. 2023 Nov;73(3):178-184. doi: 10.3164/jcbn.22-122. Epub 2023 Aug 18.

DOI:10.3164/jcbn.22-122
PMID:37970545
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10636582/
Abstract

Leucine-rich repeat kinase 2 (LRRK2) plays an important role in a variety of inflammatory diseases, as well as peripheral and central immune responses. At present, there are few reports about the role of LRRK2 in lung cancer, and need to be further explored. The main purpose of this study is to explore the role and mechanism of LRRK2 in lung cancer. The results revealed that the expression of LRRK2 was increased in the tissues of lung cancer patient and lung cancer cells. Further studies found that interference with LRRK2 expression significantly induced the apoptosis, and promoted the expression of caspase-3, caspase-9, and Bax. More importantly, si-LRRK2 inhibited the expression of VEGF and P-gp, indicating inhibition of cell proliferation and drug resistance. What's more, LRRK2 regulated TLR4/NF-κB signaling pathways and NLRP3 inflammasome, and TLR4/NF-κB pathways was involved in the molecular mechanism of LRRK2 on lung cancer cells. In conclusion, this study suggested that the mechanism of si-LRRK2 inhibiting the progression of lung cancer is to regulate the TLR4/NF-κB signaling pathways and NLRP3 inflammasome.

摘要

富含亮氨酸重复激酶2（LRRK2）在多种炎症性疾病以及外周和中枢免疫反应中发挥重要作用。目前，关于LRRK2在肺癌中的作用报道较少，有待进一步探索。本研究的主要目的是探讨LRRK2在肺癌中的作用及机制。结果显示，LRRK2在肺癌患者组织和肺癌细胞中的表达增加。进一步研究发现，干扰LRRK2表达可显著诱导细胞凋亡，并促进caspase-3、caspase-9和Bax的表达。更重要的是，si-LRRK2抑制VEGF和P-gp的表达，表明其对细胞增殖和耐药性有抑制作用。此外，LRRK2调节TLR4/NF-κB信号通路和NLRP3炎性小体，且TLR4/NF-κB通路参与LRRK2对肺癌细胞作用的分子机制。总之，本研究表明si-LRRK2抑制肺癌进展的机制是调节TLR4/NF-κB信号通路和NLRP3炎性小体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a55/10636582/3cb27755b417/jcbn22-122f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a55/10636582/1b3f170753bb/jcbn22-122f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a55/10636582/3d9b3eb9af3a/jcbn22-122f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a55/10636582/7c1a2010a825/jcbn22-122f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a55/10636582/39c79a7dc922/jcbn22-122f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a55/10636582/3cb27755b417/jcbn22-122f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a55/10636582/1b3f170753bb/jcbn22-122f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a55/10636582/3d9b3eb9af3a/jcbn22-122f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a55/10636582/7c1a2010a825/jcbn22-122f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a55/10636582/39c79a7dc922/jcbn22-122f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a55/10636582/3cb27755b417/jcbn22-122f05.jpg

相似文献

1
Knockdown of LRRK2 inhibits the progression of lung cancer by regulating TLR4/NF-κB pathways and NLRP3 inflammasome.抑制LRRK2可通过调节TLR4/NF-κB通路和NLRP3炎性小体来抑制肺癌进展。
J Clin Biochem Nutr. 2023 Nov;73(3):178-184. doi: 10.3164/jcbn.22-122. Epub 2023 Aug 18.
2
Hydrogen Sulfide Contributes to Uterine Quiescence Through Inhibition of NLRP3 Inflammasome Activation by Suppressing the TLR4/NF-κB Signalling Pathway.硫化氢通过抑制TLR4/NF-κB信号通路抑制NLRP3炎性小体激活，从而促进子宫静止。
J Inflamm Res. 2021 Jun 25;14:2753-2768. doi: 10.2147/JIR.S308558. eCollection 2021.
3
Effects of the TLR4/Myd88/NF-κB Signaling Pathway on NLRP3 Inflammasome in Coronary Microembolization-Induced Myocardial Injury.TLR4/Myd88/NF-κB信号通路对冠状动脉微栓塞诱导的心肌损伤中NLRP3炎性小体的影响
Cell Physiol Biochem. 2018;47(4):1497-1508. doi: 10.1159/000490866. Epub 2018 Jun 21.
4
Salidroside inhibits NLRP3 inflammasome activation and apoptosis in microglia induced by cerebral ischemia/reperfusion injury by inhibiting the TLR4/NF-κB signaling pathway.红景天苷通过抑制TLR4/NF-κB信号通路抑制脑缺血/再灌注损伤诱导的小胶质细胞中NLRP3炎性小体激活和凋亡。
Ann Transl Med. 2021 Nov;9(22):1694. doi: 10.21037/atm-21-5752.
5
Cattle Encephalon Glycoside and Ignotin Attenuates Aβ1-42-Mediated Neurotoxicity by Preventing NLRP3 Inflammasome Activation and Modulating Microglial Polarization via TLR4/NF-κB Signaling Pathway.牛脑苷脂和 Ignotin 通过 TLR4/NF-κB 信号通路抑制 NLRP3 炎性小体激活和调节小胶质细胞极化来减轻 Aβ1-42 介导的神经毒性。
Neurotox Res. 2022 Dec;40(6):1802-1811. doi: 10.1007/s12640-022-00585-5. Epub 2022 Oct 10.
6
Atorvastatin suppresses NLRP3 inflammasome activation via TLR4/MyD88/NF-κB signaling in PMA-stimulated THP-1 monocytes.阿托伐他汀通过 TLR4/MyD88/NF-κB 信号通路抑制 PMA 刺激的 THP-1 单核细胞中的 NLRP3 炎性体激活。
Biomed Pharmacother. 2016 Aug;82:167-72. doi: 10.1016/j.biopha.2016.04.043. Epub 2016 May 9.
7
Curcumin Represses NLRP3 Inflammasome Activation via TLR4/MyD88/NF-κB and P2X7R Signaling in PMA-Induced Macrophages.姜黄素通过TLR4/MyD88/NF-κB和P2X7R信号通路抑制佛波酯诱导的巨噬细胞中NLRP3炎性小体的激活。
Front Pharmacol. 2016 Oct 10;7:369. doi: 10.3389/fphar.2016.00369. eCollection 2016.
8
Qinhuo Shanggan oral solution resolves acute lung injury by down-regulating TLR4/NF-B signaling cascade and inhibiting NLRP3 inflammasome activation.秦艽升白口服液通过下调 TLR4/NF-B 信号通路和抑制 NLRP3 炎性小体激活来治疗急性肺损伤。
Front Immunol. 2023 Oct 25;14:1285550. doi: 10.3389/fimmu.2023.1285550. eCollection 2023.
9
Nicardipine Inhibits Priming of the NLRP3 Inflammasome via Suppressing LPS-Induced TLR4 Expression.尼卡地平通过抑制脂多糖诱导的Toll样受体4表达来抑制NLRP3炎性小体的启动。
Inflammation. 2020 Aug;43(4):1375-1386. doi: 10.1007/s10753-020-01215-y.
10
Atorvastatin inhibits renal inflammatory response induced by calcium oxalate crystals via inhibiting the activation of TLR4/NF-κB and NLRP3 inflammasome.阿托伐他汀通过抑制 TLR4/NF-κB 和 NLRP3 炎性小体的激活抑制草酸钙晶体诱导的肾脏炎症反应。
IUBMB Life. 2020 May;72(5):1065-1074. doi: 10.1002/iub.2250. Epub 2020 Feb 21.

引用本文的文献

1
TFAP2C activates PTGES through the NOTCH3 signaling pathway to affect gefitinib resistance in lung adenocarcinoma.TFAP2C通过NOTCH3信号通路激活PTGES，从而影响肺腺癌对吉非替尼的耐药性。
J Clin Biochem Nutr. 2025 Jul;77(1):1-9. doi: 10.3164/jcbn.24-104. Epub 2025 Apr 25.
2
Identification of hub genes for the diagnosis associated with heart failure using multiple cell death patterns.利用多种细胞死亡模式鉴定与心力衰竭诊断相关的枢纽基因。
ESC Heart Fail. 2025 Aug;12(4):2898-2908. doi: 10.1002/ehf2.15299. Epub 2025 Apr 10.
3
The effect of Licochalcone A on proliferation, invasion, and drug resistance of glioma cells by regulating TLR4/NF-κB signaling pathway.

本文引用的文献

1
LRRK2 regulation of immune-pathways and inflammatory disease.LRRK2 对免疫途径和炎症性疾病的调节。
Biochem Soc Trans. 2019 Dec 20;47(6):1581-1595. doi: 10.1042/BST20180463.
2
TLR4/NF-κB Signaling Induces GSDMD-Related Pyroptosis in Tubular Cells in Diabetic Kidney Disease.Toll样受体4/核因子κB信号通路诱导糖尿病肾病肾小管细胞中与Gasdermin D相关的细胞焦亡
Front Endocrinol (Lausanne). 2019 Sep 19;10:603. doi: 10.3389/fendo.2019.00603. eCollection 2019.
3
Mechanism of Probiotic VSL#3 Inhibiting NF-κB and TNF-α on Colitis through TLR4-NF-κB Signal Pathway.
甘草查尔酮A通过调节TLR4/NF-κB信号通路对胶质瘤细胞增殖、侵袭及耐药性的影响
Clinics (Sao Paulo). 2024 Dec 20;80:100542. doi: 10.1016/j.clinsp.2024.100542. eCollection 2025.
4
Investigating the role of prognostic mitophagy-related genes in non-small cell cancer pathogenesis via multiomics and network-based approach.通过多组学和基于网络的方法研究预后性线粒体自噬相关基因在非小细胞癌发病机制中的作用。
3 Biotech. 2024 Nov;14(11):273. doi: 10.1007/s13205-024-04127-y. Epub 2024 Oct 21.
益生菌VSL#3通过TLR4-NF-κB信号通路抑制结肠炎中NF-κB和TNF-α的机制
Iran J Public Health. 2019 Jul;48(7):1292-1300.
4
Non-Small Cell Lung Cancer: Epidemiology, Screening, Diagnosis, and Treatment.非小细胞肺癌：流行病学、筛查、诊断和治疗。
Mayo Clin Proc. 2019 Aug;94(8):1623-1640. doi: 10.1016/j.mayocp.2019.01.013.
5
Influences of the TLR4/NF-κB pathway on memory function and inflammatory factors in rats with cerebral small vessel disease.TLR4/NF-κB 通路对脑小血管病大鼠记忆功能及炎症因子的影响。
Eur Rev Med Pharmacol Sci. 2019 Jul;23(14):6264-6271. doi: 10.26355/eurrev_201907_18447.
6
Cancer cell-derived long pentraxin 3 (PTX3) promotes melanoma migration through a toll-like receptor 4 (TLR4)/NF-κB signaling pathway.肿瘤细胞衍生的长 pentraxin 3（PTX3）通过 toll 样受体 4（TLR4）/NF-κB 信号通路促进黑色素瘤迁移。
Oncogene. 2019 Jul;38(30):5873-5889. doi: 10.1038/s41388-019-0848-9. Epub 2019 Jun 28.
7
Downregulated LRRK2 gene expression inhibits proliferation and migration while promoting the apoptosis of thyroid cancer cells by inhibiting activation of the JNK signaling pathway.下调 LRRK2 基因表达通过抑制 JNK 信号通路的激活抑制甲状腺癌细胞的增殖和迁移，同时促进其凋亡。
Int J Oncol. 2019 Jul;55(1):21-34. doi: 10.3892/ijo.2019.4816. Epub 2019 May 29.
8
Lung Cancer.肺癌。
Med Clin North Am. 2019 May;103(3):463-473. doi: 10.1016/j.mcna.2018.12.006.
9
Hesperetin, a Citrus Flavonoid, Attenuates LPS-Induced Neuroinflammation, Apoptosis and Memory Impairments by Modulating TLR4/NF-κB Signaling.橙皮素，一种柑橘类黄酮，通过调节 TLR4/NF-κB 信号通路来减轻 LPS 诱导的神经炎症、细胞凋亡和记忆损伤。
Nutrients. 2019 Mar 17;11(3):648. doi: 10.3390/nu11030648.
10
NLRP3 Inflammasome: A Possible Link Between Obesity-Associated Low-Grade Chronic Inflammation and Colorectal Cancer Development.NLRP3 炎性小体：肥胖相关低度慢性炎症与结直肠癌发展之间的可能联系。
Front Immunol. 2018 Dec 11;9:2918. doi: 10.3389/fimmu.2018.02918. eCollection 2018.