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TGF-β通过激活smad2信号通路上调CXCR4表达促进非小细胞肺癌A549细胞迁移和侵袭
作者:李汉杰  葛鹏  景瑞军  陈鑫  李建华 
单位:西安医学院第二附属医院 心胸外科, 陕西 西安 710038
关键词:转化生长因子β 趋化因子受体4 非小细胞肺癌 迁移 侵袭 
分类号:R734.2
出版年·卷·期(页码):2019·47·第五期(555-560)
摘要:

目的:探索TGF-β是否能够通过上调超化因子受体4(CXCR4)的表达而促进非小细胞肺癌的迁移和侵袭,并证实该效应是否与smad2信号相关。方法:常规培养肺癌A549细胞后,通过Transwell迁移小室观察10 ng·ml-1的TGF-β对肺癌细胞迁移和侵袭能力影响。通过蛋白印迹和qPCR法检测10 ng·ml-1的TGF-β处理细胞后CXCR4的表达情况,采取蛋白印迹法检测smad2激活情况。使用TGF-β/smad信号通路抑制剂LY2109761,检测CXCR4的表达以及肺癌细胞迁移和侵袭能力。结果:10 ng·ml-1的TGF-β显著提升肺癌A549细胞迁移和侵袭能力(P<0.05),同时10 ng·ml-1的TGF-β处理后显著提升CXCR4的表达水平和smad2的活化水平(P<0.05)。使用smad信号通路抑制剂LY2109761作用后,细胞CXCR4的表达水平和smad2的活化水平显著降低(P<0.05)。结论:TGF-β能够通过上调CXCR4的表达而促进非小细胞肺癌的迁移和侵袭,该效应可能与TGF-β激活了smad2信号相关。

Objective:To explore whether TGF-β can promote the migration and invasion of non-small cell lung cancer by up-regulating the expression of CXCR4 and confirm whether this effect is associated with smad2 signaling. Methods:After cultured lung cancer A549 cells, the effect of 10 ng·ml-1 TGF-β on the migration and invasion of lung cancer cells was observed by Transwell migration chamber. The expression of CXCR4 was detected by Western blotting and qPCR method after 10 ng·ml-1 of TGF-β-treated cells. The activation of smad2 was detected by Western blotting. The expression of CXCR4 and the migration and invasion ability of lung cancer cells were examined by usingTGF-β/smad signaling pathway inhibitor LY2109761. Results:10 ng·ml-1 of TGF-β significantly increased the migration and invasion of lung cancer A549 cells. At the same time, 10 ng·ml-1 TGF-β treatment significantly increased the expression level of CXCR4 and the activation level of smad2. After treatment with the smad signaling pathway inhibitor LY2109761, the expression level of CXCR4 and the ability to migrate and invade were significantly reduced. Conclusion:TGF-β can promote the migration and invasion of non-small cell lung cancer by up-regulating the expression of CXCR4, which may be related to the activation of smad2 signaling by TGF-β.

参考文献:

[1] CARRERAS-TORRES R,JOHANSSON M,HAYCOCK P C,et al.Obesity,metabolic factors and risk of different histological types of lung cancer:a mendelian randomization study[J].PLoS One,2017,12(6):54-60.
[2] SZABO E,MAO J T,LAM S,et al.Chemoprevention of lung cancer:diagnosis and management of lung cancer,3rd ed:American College of Chest Physicians evidence-based clinical practice guidelines[J].Chest,2013,143(5 Suppl):e40S-60S.
[3] MASTERS G A,TEMIN S,AZZOLI C G,et al.Systemic therapy for stage IV non-small-cell lung cancer:American Society of Clinical Oncology clinical practice guideline update[J].J Clin Oncol,2015,33(30):3488-3515.
[4] 管超,黄鲁众,于莉,等.78例小细胞肺癌患者脑转移发生时间的相关因素初步研究[J].现代医学,2017,45(11):1642-1645.
[5] FARHAT F S,HOUHOU W.Targeted therapies in non-small cell lung carcinoma:what have we achieved so far[J].Ther Adv Med Oncol,2013,5(4):249-270.
[6] LEMJABBAR-ALAOUI H,HASSAN O,YANG Y W,et al.Lung cancer:biology and treatment options[J].Biochim Biophys Acta,2015,1856(2):189-210.
[7] WU X,WU G,YAO X,et al.The clinicopathological significance and ethnic difference of FHIT hypermethylation in non-small-cell lung carcinoma:a meta-analysis and literature review[J].Drug Des Devel Ther,2016,10:699-709.
[8] FUJIMOTO J,WISTUBA I I.Current concepts on the molecular pathology of non-small cell lung carcinoma[J].Semin Diagn Pathol,2014,31(4):306-313.
[9] SOBOLIK T,YJ S,WELLS S,et al.CXCR4 drives the metastatic phenotype in breast cancer through induction of CXCR2 and activation of MEK and PI3K pathways[J].Mol Biol Cell,2014,25(5):566-582.
[10] DÖRING Y,PAWIG L,WEBER C,et al.The CXCL12/CXCR4 chemokine ligand/receptor axis in cardiovascular disease[J].Front Physiol,2014,33(4):309-316.
[11] 金晶,李镭,李为民.影响肺癌转移部位的临床因素分析[J].华西医学,2018,33(1):41-46.
[12] 许阳,杨震,李春笋,等.肺癌转移相关蛋白1相互作用蛋白的筛选及验证[J].解放军医学院学报,2018,39(5):432-436.
[13] XM Z,HE L,HOU G,et al.Clinicopathological significance of CXCR4 in non-small cell lung cancer[J].Drug Des Devel Ther,2015,9:1349-1358.
[14] LIANG Z,BIAN X,SHIM H.Inhibition of breast cancer metastasis with microRNA-302a by downregulation of CXCR4 expression[J].Breast Cancer Res Treat,2014,146(3):535-542.
[15] ZHANG C,LI J,HAN Y,et al.A meta-analysis for CXCR4 as a prognostic marker and potential drug target in non-small cell lung cancer[J].Drug Des Devel Ther,2015,9:3267-3278.
[16] WALD O,SHAPIRA O M,IZHAR U.CXCR4/CXCL12 axis in non small cell lung cancer (NSCLC) pathologic roles and therapeutic potential[J].Theranostics,2013,3(1):26-33.
[17] 熊海林,孙爱华,周思维.联合检测CXCR4与E-Cad在非小细胞肺癌中的表达与脑转移的相关性研究[J].现代诊断与治疗,2017,28(1):1-3.
[18] 廖悄,王任华,程兰,等.肺癌组织中SDF-1和CXCR4蛋白表达及对肺癌细胞生物学特性的影响[J].肿瘤药学,2017,7(2):179-182,247.
[19] GORDIAN E,LI J,PEVZNER Y,et al.Transforming growth factor β signaling overcomes dasatinib resistance in lung cancer[J].PLoS One,2014,9(12):131-137.
[20] HAQUE S,MORRIS J C.Transforming growth factor-β:a therapeutic target for cancer[J].Hum Vaccin Immunother,2017,13(8):1741-1750.
[21] 建华,韩玲,杨志良.miR-125b通过靶向致癌基因LIN28B调控肝细胞癌细胞的增殖和侵袭行为[J].实用肿瘤杂志,2018,33(2):128-132.
[22] CHOI Y H,BURDICK M D,STRIETER B A,et al.CXCR4,but not CXCR7,discriminates metastatic behavior in non-small cell lung cancer cells[J].Mol Cancer Res,2014,12(1):38-47.
[23] CODA D M,GAARENSTROOM T,EAST P,et al.Distinct modes of SMAD2 chromatin binding and remodeling shape the transcriptional response to NODAL/activin signaling[J].Elife,2017,6:1211-1217.

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