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浙江大学学报(医学版)  2018, Vol. 47 Issue (6): 659-664    DOI: 10.3785/j.issn.1008-9292.2018.12.15
综述     
白介素6在肺癌中的作用研究进展
唐和孝(),白玉泉,申武林,赵金平*()
武汉大学中南医院胸心血管外科, 湖北 武汉 430071
Research progress on interleukin-6 in lung cancer
TANG Hexiao(),BAI Yuquan,SHEN Wulin,ZHAO Jinping*()
Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
 全文: PDF(1015 KB)   HTML( 12 )
摘要:

T细胞作为细胞免疫疗法的核心,在肺癌研究及治疗中占据着重要地位。IL-6是目前已知的肺癌干细胞直接靶向的重要T细胞共刺激信号因子,其作为肺癌细胞中高表达的细胞因子,在肿瘤的发生、发展、侵袭、转移等一系列生物学行为中发挥着重要作用。本文对近年来IL-6在肺癌领域的研究进展,包括IL-6在肺癌发生和进展中的作用及其在肺癌治疗敏感性中的作用进行了综述。

关键词: 白细胞介素6肺肿瘤综述    
Abstract:

As the core of cellular immunotherapy, T cells are important aspects of research and treatment of lung cancer. IL-6 is a costimulatory signal factor of T cells that is directly targeted by lung cancer stem cells. As a highly expressed cytokine in lung cancer cells, IL-6 plays an important role in variety of biological activities such as tumor occurrence, development, invasion and metastasis. This article reviews the research progress on IL-6 in lung cancer, including cancer development and progression, and the therapeutic sensitivity of lung cancer.

Key words: Interleukin-6    Lung neoplasms    Review
收稿日期: 2018-05-20 出版日期: 2019-03-15
:  R734.2  
基金资助: 国家自然科学基金(81501985)
通讯作者: 赵金平     E-mail: thx1245@sina.com;zhaojpthx@126.com
作者简介: 唐和孝(1985-), 男, 博士, 主治医师, 主要从事肺癌领域的雌激素、IL-6等相关功能和机制的研究; E-mail:thx1245@sina.com; https://orcid.org/0000-0002-9675-9200
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引用本文:

唐和孝,白玉泉,申武林,赵金平. 白介素6在肺癌中的作用研究进展[J]. 浙江大学学报(医学版), 2018, 47(6): 659-664.

TANG Hexiao,BAI Yuquan,SHEN Wulin,ZHAO Jinping. Research progress on interleukin-6 in lung cancer. J Zhejiang Univ (Med Sci), 2018, 47(6): 659-664.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2018.12.15        http://www.zjujournals.com/med/CN/Y2018/V47/I6/659

1 HAMRA G B , RICHARDSON D B , DEMENT J et al. Lung cancer risk associated with regulated and unregulated chrysotile asbestos fibers[J]. Epidemiology, 2017, 28 (2): 275- 280
doi: 10.1097/EDE.0000000000000597
2 HRADILOVA N , SADILKOVA L , PALATA O et al. Generation of dendritic cell-based vaccine using high hydrostatic pressure for non-small cell lung cancer immunotherapy[J]. PLoS One, 2017, 12 (2): e0171539
doi: 10.1371/journal.pone.0171539
3 SHEN M , REN X . Highlights on immune checkpoint inhibitors in non-small cell lung cancer[J]. Tumour Biol, 2017, 39 (3): 1010428317695013
4 KARASAKI T , NAGAYAMA K , KUWANO H et al. An immunogram for the cancer-immunity cycle:towards personalized immunotherapy of lung cancer[J]. J Thorac Oncol, 2017, 12 (5): 791- 803
doi: 10.1016/j.jtho.2017.01.005
5 张静, 张振安 . IL-6、IFN-γ、TNF-α、NKG2D在晚期肺癌患者中的表达及意义[J]. 疑难病杂志, 2015, 14 (5): 483- 486
ZHANG Jing , ZHANG Zhen'an . Expression of serum IL-6, IFN-γ, TNF-α and NKG2D in patients with lung cancer and its clinical significance[J]. Chinese Journal of Difficult and Complicated Cases, 2015, 14 (5): 483- 486
doi: 10.3969/j.issn.1671-6450.2015.05.012
6 YOUNG R P , HOPKINSR J . The mevalonate pathway and innate immune hyper-responsiveness in the pathogenesis of COPD and lung cancer:potential for chemoprevention[J]. Curr Mol Pharmacol, 2017, 10 (1): 46- 59
doi: 10.2174/1874467209666160112130016
7 李娟, 曾诚, 刘冰 et al. A549细胞中NOX4介导IL-6自分泌及细胞侵袭的研究[J]. 广东药学院学报, 2015, 31 (3): 403- 406, 419
LI Juan , ZENG Cheng , LIU Bing et al. Effect of NOX4 on IL-6 autocrine and cell invasion in A549 cells[J]. Journal of Guangdong Pharmaceutical University, 2015, 31 (3): 403- 406, 419
doi: 10.3969/j.issn.1006-8783.2015.03.026
8 KISHIMOTO T . Interleukin-6:discovery of a pleiotropic cytokine[J]. Arthritis Res Ther, 2006, 8 (Suppl 2): S2
9 WANG X , YANG X , TSAI Y et al. IL-6 mediates macrophage infiltration after irradiation via up-regulation of CCL2/CCL5 in non-small cell lung cancer[J]. Radiat Res, 2017, 187 (1): 50- 59
doi: 10.1667/RR14503.1
10 HSU H S , LIN J H , HSU T W et al. Mesenchymal stem cells enhance lung cancer initiation through activation of IL-6/JAK2/STAT3 pathway[J]. Lung Cancer, 2012, 75 (2): 167- 177
11 CHUANG C H , GREENSIDE P G , ROGERS Z N et al. Molecular definition of a metastatic lung cancer state reveals a targetable CD109-Janus kinase-Stat axis[J]. Nat Med, 2017, 23 (3): 291- 300
doi: 10.1038/nm.4285
12 CHANG Q , BOURNAZOU E , SANSONE P et al. The IL-6/JAK/Stat3 feed-forward loop drives tumorigenesis and metastasis[J]. Neoplasia, 2013, 15 (7): 848- 862
doi: 10.1593/neo.13706
13 CHAMORRO A , REVILLA M , OBACH V et al. The -174G/C polymorphism of the interleukin 6 gene is a hallmark of lacunar stroke and not other ischemic stroke phenotypes[J]. Cerebrovasc Dis, 2005, 19 (2): 91- 95
doi: 10.1159/000082785
14 KITAMURA A , HASEGAWA G , OBAYASHI H et al. Interleukin-6 polymorphism (-634C/G) in the promotor region and the progression of diabetic nephropathy in type 2 diabetes[J]. Diabet Med, 2002, 19 (12): 1000- 1005
doi: 10.1046/j.1464-5491.2002.00844.x
15 ZHOU B , LIU J , WANG Z M et al. C-reactive protein, interleukin 6 and lung cancer risk:a meta-analysis[J]. PLoS One, 2012, 7 (8): e43075
doi: 10.1371/journal.pone.0043075
16 WANG W , CHEN J , ZHAO F et al. Lack of association between a functional polymorphism (rs1800796) in the interleukin-6 gene promoter and lung cancer[J]. Diagn Pathol, 2014, 9:134
doi: 10.1186/1746-1596-9-134
17 LIU Y , SONG X L , ZHANG G L et al. Lack of association between IL-6-174G>C polymorphism and lung cancer:a meta-analysis[J]. Genet Mol Res, 2015, 14 (1): 163- 169
doi: 10.4238/2015.January.15.19
18 CROHNS M , SAARELAINEN S , LAINE S et al. Cytokines in bronchoalveolar lavage fluid and serum of lung cancer patients during radiotherapy-Association of interleukin-8 and VEGF with survival[J]. Cytokine, 2010, 50 (1): 30- 36
doi: 10.1016/j.cyto.2009.11.017
19 GIANNITRAPANI L , SORESI M , BALASUS D et al. Genetic association of interleukin-6 polymorphism (-174 G/C) with chronic liver diseases and hepatocellular carcinoma[J]. World J Gastroenterol, 2013, 19 (16): 2449- 2455
doi: 10.3748/wjg.v19.i16.2449
20 JIA W , FEI G H , HU J G et al. A study on the effect of IL-6 gene polymorphism on the prognosis of non-small-cell lung cancer[J]. Onco Targets Ther, 2015, 8:2699- 2704
21 宿濛, 周宝森 . IL-6和IL-1β单核苷酸多态性与非吸烟女性肺癌易感性的关系[J]. 中国肺癌杂志, 2014, 17 (8): 612- 617
SU Meng , ZHOU Baosen . Association of genetic polymorphisms in IL-6 and IL-1β gene with risk of lung cancer in female non-smokers[J]. Chinese Journal of Lung Cancer, 2014, 17 (8): 612- 617
22 ZHU X J, LI W Z, LI H, et al. Association of interleukin-6 gene polymorphisms and circulating levels with keloid scars in a Chinese Han population[J/OL]. Genet Mol Res, 2017, 16(2):gmr16029110.
23 LEE S O , YANG X , DUAN S et al. IL-6 promotes growth and epithelial-mesenchymal transition of CD133+ cells of non-small cell lung cancer[J]. Oncotarget, 2016, 7 (6): 6626- 6638
24 姜伊娜.ATM/NF-kappaB通路在IL-6促肺癌细胞上皮间质转换并增强转移的作用研究[D].厦门: 厦门大学, 2015.
JIANG Yina. IL-6 promotes epithelial-mesenchymal transition and increases metastasis in lung cancer cells via the activation of ATM/NF-kappaB pathway[D]. Xiamen: Xiamen University, 2015. (in Chinese)
25 QU Z , SUN F , ZHOU J et al. Interleukin-6 prevents the initiation but enhances the progression of lung cancer[J]. Cancer Res, 2015, 75 (16): 3209- 3215
doi: 10.1158/0008-5472.CAN-14-3042
26 CHEN Y , ZHANG F , TSAI Y et al. IL-6 signaling promotes DNA repair and prevents apoptosis in CD133+ stem-like cells of lung cancer after radiation[J]. Radiat Oncol, 2015, 10:227
doi: 10.1186/s13014-015-0534-1
27 KUDO M , JONO H , SHINRIKI S et al. Antitumor effect of humanized anti-interleukin-6 receptor antibody (tocilizumab) on glioma cell proliferation. Laboratory investigation[J]. J Neurosurg, 2009, 111 (2): 219- 225
28 JIANG Y N , YAN H Q , HUANG X B et al. Interleukin 6 trigged ataxia-telangiectasia mutated activation facilitates lung cancer metastasis via MMP-3/MMP-13 up-regulation[J]. Oncotarget, 2015, 6 (38): 40719- 40733
29 LIU C C , LIN J H , HSU T W et al. IL-6 enriched lung cancer stem-like cell population by inhibition of cell cycle regulators via DNMT1 upregulation[J]. Int J Cancer, 2015, 136 (3): 547- 559
30 LI L , HAN R , XIAO H et al. Metformin sensitizes EGFR-TKI-resistant human lung cancer cells in vitro and in vivo through inhibition of IL-6 signaling and EMT reversal[J]. Clin Cancer Res, 2014, 20 (10): 2714- 2726
doi: 10.1158/1078-0432.CCR-13-2613
31 HAURA E B , LIVINGSTON S , COPPOLA D . Autocrine interleukin-6/interleukin-6 receptor stimulation in non-small-cell lung cancer[J]. Clin Lung Cancer, 2006, 7 (4): 273- 275
doi: 10.3816/CLC.2006.n.006
32 KITA H , SHIRAISHI Y , WATANABE K et al. Does postoperative serum interleukin-6 influence early recurrence after curative pulmonary resection of lung cancer?[J]. Ann Thorac Cardiovasc Surg, 2011, 17 (5): 454- 460
doi: 10.5761/atcs.oa.10.01627
33 LIAO C , YU Z , GUO W et al. Prognostic value of circulating inflammatory factors in non-small cell lung cancer:a systematic review and meta-analysis[J]. Cancer Biomark, 2014, 14 (6): 469- 481
doi: 10.3233/CBM-140423
34 闫凌丽 . PCT、TNF-α、IL-6、IL-8在胸腔积液诊断中的应用价值[J]. 临床肺科杂志, 2016, 21 (11): 2071- 2073
YAN Lingli . Application value of PCT, TNF-α, IL-6 and IL-8 in the diagnosis of pleural effusion[J]. Journal of Clinical Pulmonary Medicine, 2016, 21 (11): 2071- 2073
doi: 10.3969/j.issn.1009-6663.2016.11.038
35 闫凌丽, 吕志宇 . PCT、CRP、IL-6、IL-8在胸腔积液中的鉴别诊断价值[J]. 四川医学, 2016, 37 (10): 1137- 1139, 1140
YAN Lingli , LYU Zhiyu . Value of PCT, CRP, IL-6, IL-8 in differential diagnosis of pleural effusion[J]. Sichuan Medical Journal, 2016, 37 (10): 1137- 1139, 1140
36 TANIGUCHI K , KARIN M . IL-6 and related cytokines as the critical lynchpins between inflammation and cancer[J]. Semin Immunol, 2014, 26 (1): 54- 74
37 CHAN N , WILLIS A , KORNHAUSER N et al. Influencing the tumor microenvironment:a phase Ⅱ study of copper depletion using tetrathiomolybdate in patients with breast cancer at high risk for recurrence and in preclinical models of lung metastases[J]. Clin Cancer Res, 2017, 23 (3): 666- 676
doi: 10.1158/1078-0432.CCR-16-1326
38 HARADA D , TAKIGAWA N , KIURA K . The role of STAT3 in non-small cell lung cancer[J]. Cancers(Basel), 2014, 6 (2): 708- 722
39 WANG X , WANG Y , XIAO G et al. Hypermethylated in cancer 1(HIC1) suppresses non-small cell lung cancer progression by targeting interleukin-6/Stat3 pathway[J]. Oncotarget, 2016, 7 (21): 30350- 30364
40 CHANG C H , HSIAO C F , YEH Y M et al. Circulating interleukin-6 level is a prognostic marker for survival in advanced nonsmall cell lung cancer patients treated with chemotherapy[J]. Int J Cancer, 2013, 132 (9): 1977- 1985
doi: 10.1002/ijc.v132.9
41 裴宝祥.肿瘤微环境CSF-1, IL-6及TAMs对NSCLC患者预后的作用[D].天津: 天津医科大学, 2015.
PEI Baoxiang. The role of tumor microenvironment CSF-1, IL-6 and TAMs in the prognosis of patients with NSCLC[D]. Tianjin: Tianjin Medical University, 2015. (in Chinese)
42 YAN H Q , HUANG X B , KE S Z et al. Interleukin 6 augments lung cancer chemotherapeutic resistance via ataxia-telangiectasia mutated/NF-kappaB pathway activation[J]. Cancer Sci, 2014, 105 (9): 1220- 1227
doi: 10.1111/cas.2014.105.issue-9
43 BANIK D , NETHERBY C S , BOGNER P N et al. MMP3-mediated tumor progression is controlled transcriptionally by a novel IRF8-MMP3 interaction[J]. Oncotarget, 2015, 6 (17): 15164- 15179
44 KUDO Y , IIZUKA S , YOSHIDA M et al. Matrix metalloproteinase-13(MMP-13) directly and indirectly promotes tumor angiogenesis[J]. J Biol Chem, 2012, 287 (46): 38716- 38728
doi: 10.1074/jbc.M112.373159
45 任涛.APE1介导IL-6/STAT3信号调控肺癌A549细胞对CDDP的化疗敏感性[D].重庆: 第三军医大学, 2015.
REN Tao. APE1 mediates IL-6/STAT3 signaling and regulates chemosensitivity of lung cancer A549 cells to CDDP[D]. Chongqing: Third Military Medical University, 2015. (in Chinese)
46 ZHANG F , DUAN S , TSAI Y et al. Cisplatin treatment increases stemness through upregulation of hypoxia-inducible factors by interleukin-6 in non-small cell lung cancer[J]. Cancer Sci, 2016, 107 (6): 746- 754
doi: 10.1111/cas.2016.107.issue-6
47 梁文龙 . TNF-β联合IL-6检测对早期诊断非小细胞肺癌术后放疗导致的放射性肺炎的初探[J]. 齐齐哈尔医学院学报, 2015, 36 (26): 3971- 3973
LIANG Wenlong . Detection of TNF-β combined with IL-6 in the early diagnosis of radiation-induced pneumonia caused by postoperative radiotherapy for non-small cell lung cancer[J]. Journal of Qiqihar University of Medicine, 2015, 36 (26): 3971- 3973
48 DUAN S , TSAI Y , KENG P et al. IL-6 signaling contributes to cisplatin resistance in non-small cell lung cancer via the up-regulation of anti-apoptoticand DNA repair associated molecules[J]. Oncotarget, 2015, 6 (29): 27651- 27660
49 LIU X L , ZHANG X T , MENG J et al. ING5 knockdown enhances migration and invasion of lung cancer cells by inducing EMT via EGFR/PI3K/Akt and IL-6/STAT3 signaling pathways[J]. Oncotarget, 2017, 8 (33): 54265- 54276
50 REN T , SHAN J , QING Y et al. Sequential treatment with AT-101 enhances cisplatin chemosensitivity in human non-small cell lung cancer cells through inhibition of apurinic/apyrimidinic endonuclease 1-activated IL-6/STAT3 signaling pathway[J]. Drug Des Devel Ther, 2014, 8:2517- 2529
51 PATEL R T , DEEN K I , YOUNGS D et al. Interleukin 6 is a prognostic indicator of outcome in severe intra-abdominal sepsis[J]. Br J Surg, 1994, 81 (9): 1306- 1308
doi: 10.1002/(ISSN)1365-2168
52 YAMASHITA K , FUJINAGA T , MIYAMOTO T et al. Canine acute phase response:relationship between serum cytokine activity and acute phase protein in dogs[J]. J Vet Med Sci, 1994, 56 (3): 487- 492
doi: 10.1292/jvms.56.487
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