|Table of Contents|

SIRT3 regulates the NF-κB pathway inhibiting lung cancer cell metastasis and inflammatory response under hypoxia

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 24
Page:
4508-4514
Research Field:
Publishing date:

Info

Title:
SIRT3 regulates the NF-κB pathway inhibiting lung cancer cell metastasis and inflammatory response under hypoxia
Author(s):
HUANG Bo1; 2; DING Jie1; GUO Hongrong1; WANG Hongjuan1; XU Jianqun1; ZHENG Quan1
1.Wuhan Third Hospital/Tongren Hospital of Wuhan University,Hubei Wuhan 430074,China;2.Wuhan East Lake High-Tech Development Zone Jiufeng Street Center City Community Health Service Center,Hubei Wuhan 430075,China.
Keywords:
lung cancer; hypoxic environment; SIRT3 overexpression; NF-κB pathway; inflammatory response
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2023.24.004
Abstract:
Objective:To investigate the effect of silent information regulator 3 (SIRT3) overexpression regulating nuclear factor-κB (NF-κB) pathway on cellular inflammatory response,migration and invasion in lung cancer cells under hypoxic conditions.Methods:Based on A549 lung cancer cells,overexpressed and null lentiviral transfected lung cancer cells were constructed according to the sequence of SIRT3,and untransfected cells were used as controls and exposed to normoxic (21%O2) and hypoxic (5%~8%O2) conditions in culture to verify the feasibility of the experiment.The cells were divided into normoxia,hypoxia,JSH-23 (NF-κB transcriptional activity inhibitor),SIRT3 overexpression,and JSH-23+SIRT3 overexpression groups according to the treatments.cell proliferation was detected by MTT,cell invasion by Transwell,cell migration by cell scratching,and protein MMP-2,ICAM-1,SIRT3 and p-NF-κB p65 by Western-blot.qPCR was performed to detect the mRNA expression of SIRT3 and p-NF-κB p65 in the cells,and ELISA was performed to detect the content of IL-1β,TNF-α and IL-6 in the cells.Results:Compared with the normoxia group,cell proliferation ability increased (P＜0.05),invasion and migration ability increased (P＜0.05),MMP-2,ICAM-1 and p-NF-κB p65 protein expression was upregulated (P＜0.05),mRNA expression of p-NF-κB p65 was upregulated (P＜0.05),SIRT3 mRNA and protein expression was downregulated (P＜0.05),and IL-1β,TNF-α and IL-6 levels were increased (P＜0.05).Compared with the hypoxic group,the JSH-23 group and SIRT3 overexpression group showed decreased cell proliferation,invasion and migration ability (P＜0.05),down-regulation of MMP-2,ICAM-1 and p-NF-κB p65 protein expression (P＜0.05),down-regulation of p-NF-κB p65 mRNA expression (P＜0.05),and SIRT3 mRNA and protein expression was upregulated (P＜0.05),and IL-1β,TNF-α and IL-6 levels were decreased (P＜0.05).The trend of change was more significant in the JSH-23+SIRT3 overexpression group compared with the JSH-23 group (P＜0.05).Conclusion:SIRT3 inhibits the NF-κB pathway under hypoxic conditions,thereby suppressing the inflammatory response and progression of lung cancer cells.

References:

［1］ PAPAVASSILIOU KA,PAPAVASSILIOU AG.The biology and therapeutic Potential of the Src-YAP axis in non-small cell lung cancer (NSCLC)［J］.Cancers,2022,14(24):6178.
［2］ ZHU X,KUDO M,HUANG X,et al.Frontiers of microRNA signature in non-small cell lung cancer［J］.Front Cell Dev Biol,2021,9:643942.
［3］ ALLEGRA A,INNAO V,POLITO F,et al.SIRT2 and SIRT3 expression correlates with redox imbalance and advanced clinical stage in patients with multiple myeloma［J］.Clin Biochem,2021,93:42-49.
［4］ CAO Y,LI P,WANG H,et al.SIRT3 promotion reduces resistance to cisplatin in lung cancer by modulating the FOXO3/CDT1 axis［J］.Cancer Med,2021,10(4):1394-1404.
［5］ TANG X,LI Y,LIU L,et al.Sirtuin 3 induces apoptosis and necroptosis by regulating mutant p53 expression in small cell lung cancer［J］.Oncol Rep,2020,43(2):591-600.
［6］ CHEN C,GU J,WANG J,et al.Physcion 8-O-β-glucopyranoside ameliorates liver fibrosis through inflammation inhibition by regulating SIRT3-mediated NF-κB P65 nuclear expression［J］.Int Immunopharmacol,2021,90:107206.
［7］ DIMITRAKOPOULOS F,KOTTOROU A,KALOFONOU M,et al.The fire within:NF-κB involvement in non-small cell lung cancer［J］.Cancer Res,2020,80(19):4025-4036.
［8］ LI Y,SONG X,NIU J,et al.Pentraxin 3 acts as a functional effector of Akt/NF-κB signaling to modulate the progression and cisplatin-resistance in non-small cell lung cancer［J］.Arch Biochem Biophys,2021,701:108818.
［9］ ZIOLKOWSKA-SUCHANEK I,PODRALSKA M,ZURAWEK M,et al.Hypoxia-induced FAM13A regulates the proliferation and metastasis of non-small cell lung cancer cells［J］.Int J Mol Sci,2021,22(9):4302.
［10］ 马建梅,陈承,张星星,等.PEDF下调HIF-1α表达抑制缺氧状态下NSCLC细胞增殖、迁移的作用机制［J］.现代肿瘤医学,2019,27(17):3005-3009. MA JM,CHEN C,ZHANG XX,et al.The mechanism of PEDF down-regulating HIF-1α expression inhibiting proliferation and migration of NSCLC cells under hypoxia［J］.Modern Oncology,2019,27(17):3005-3009.
［11］ KUTKOWSKA J,STRZADALA L,RAPAK A.Hypoxia increases the apoptotic response to betulinic acid and betulin in human non-small cell lung cancer cells［J］.Chem Biol Interact,2021,333:109320.
［12］ SALINASV,GALLARDOR,RUIZG,et al.The role of hypoxia in endometrial cancer［J］.Curr Pharm Biotechnol,2022,23(2):221-234.
［13］ 曹静,曾宪旭,雷冬梅,等.低氧对非小细胞肺癌细胞PDHA1表达及生物学行为的影响［J］.郑州大学学报(医学版),2022,57(03):340-344. CAO J,ZENG XX,LEI DM,et al.Effects of hypoxia on PDHA1 expression and biological behaviors of non-small cell lung cancer cells［J］.Journal of Zhengzhou University(Medical Sciences),2022,57(03):340-344.
［14］ GU Y,KIM J,NA J,et al.Mitochondrial metabolic reprogramming by SIRT3 regulation ameliorates drug resistance in renal cell carcinoma［J］.Plos One,2022,17(6):e0269432.
［15］ 贾皑，张璐，任莉，等.Sirt3对肝癌细胞增殖与侵袭的影响［J］.现代肿瘤医学，2018,26（19）：3017-3021. JIA A,ZHANG L,REN L,et al.Effect of Sirt3 on the proliferation and invasion in hepatocellular carcinoma cells［J］.Modern Oncology,2018,26（19）：3017-3021.
［16］ OUYANG S,ZHANG Q,LOU L,et al.The double-edged sword of SIRT3 in cancer and its therapeutic applications［J］.Front Pharmacol,2022,13:871560.
［17］ CHENG L,ZHANG D,YAN W.Ultrasound targeted microbubble destruction mediated overexpression of Sirtuin 3 inhibits the progression of ovarian cancer［J］.Oncol Rep,2021,46(4):220.
［18］ REN G,MA Y,WANG X,et al.Aspirin blocks AMPK/SIRT3-mediated glycolysis to inhibit NSCLC cell proliferation［J］.Eur J Pharmacol,2022,932:175208.
［19］ ZHANG J,VEERAMACHANENI N.Targeting interleukin-1β and inflammation in lung cancer［J］.Biomark Res,2022,10(1):5.
［20］ HU J,LI X,YANG L,et al.Hypoxia,a key factor in the immune microenvironment［J］.Biomed Pharmacother,2022,151:113068.
［21］ TAN Z,XUE H,SUN Y,et al.The role of tumor inflammatory microenvironment in lung cancer［J］.Front Pharmacol,2021,12:688625.
［22］ 朱帅旗,段海潇,汪洋,等.NF-κB在非小细胞肺癌中的作用及治疗研究［J］.生命科学,2022,34(4):409-419. ZHU SQ,DUAN HX,WANG Y,et al.Research on the role and treatment of NF-κB in non-small cell lung cancer［J］.Chinese Bulletin of Life Sciences,2022,34(4):409-419.

Memo

Memo:
湖北省卫生健康委员会科研项目基金（编号：WJ2021F005）；湖北省武汉市卫生健康委员会医学科研项目基金（编号：WX21Q43）；武汉中青年医学骨干人才培养工程（编号：武卫通［2019］87号）
Last Update: 1900-01-01