NFATc1对人肺腺癌细胞增殖、凋亡和侵袭能力的影响

doi:10.11904/j.issn.1002-3070.2021.05.003

实用肿瘤学杂志 ›› 2021, Vol. 35 ›› Issue (5): 402-407.doi: 10.11904/j.issn.1002-3070.2021.05.003

NFATc1对人肺腺癌细胞增殖、凋亡和侵袭能力的影响

任凤海, 朱开彬, 王彦博, 周福成, 庞赛楠, 陈澜涛

哈尔滨医科大学附属肿瘤医院胸外科(哈尔滨 150081)

收稿日期:2020-12-01 修回日期:2021-03-31 出版日期:2021-10-28 发布日期:2021-10-25
通讯作者: 陈澜涛,E-mail:chenlantao198231@163.com
作者简介:任凤海,男,(1981-),硕士,主治医师,从事肺癌转移相关基因的研究。
基金资助:
2018年度黑龙江省省属高等学校基本科研业务费科研项目(编号:2018-KYYWF-0539)

Effects of NFATc1 on the proliferation,apoptosis and invasion of human lung adenocarcinoma cells

REN Fenghai, ZHU Kaibin, WANG Yanbo, ZHOU Fucheng, PANG Sainan, CHEN Lantao

Department of Thoracic Surgery,Harbin Medical University Cancer Hospital,Harbin 150081,China

Received:2020-12-01 Revised:2021-03-31 Online:2021-10-28 Published:2021-10-25

摘要/Abstract

摘要： 目的探究NFATc1对肺腺癌NCI-H1299细胞增殖、凋亡、迁移和侵袭能力的影响,以及NFATc1发挥作用的生物学机制。方法通过Realtime PCR检测NFATc1在三种肺腺癌细胞系中的相对表达水平,利用慢病毒载体构建稳定敲减NFATc1的NCI-H1299细胞系。MTT检测NFATc1对细胞增殖能力的影响,平板克隆形成实验检测NFATc1对克隆形成能力的影响,Transwell检测NFATc1对细胞迁移和侵袭能力的影响,流式细胞术检测NFATc1对细胞周期和凋亡的影响,Western blot检测NFATc1对凋亡、EMT相关蛋白和MAPK信号通路蛋白表达的影响。结果肺腺癌NCI-H1299细胞系中NFATc1表达水平相对较高。沉默NFATc1表达可以显著抑制细胞增殖(P＜0.05)、克隆形成(P＜0.05)、迁移(P＜0.05)和侵袭(P＜0.05)能力,抑制细胞周期在G1期(P＜0.05),促进细胞凋亡(P＜0.05)。Bax、Cleaved caspase-3和E-Cadherin蛋白表达增加(P＜0.05),CDK4、c-Myc、ERK、p-ERK和N-Cadherin蛋白表达降低(P＜0.05)。结论在人肺腺癌NCI-H1299细胞中抑制NFATc1表达,可以显著抑制细胞增殖、细胞周期、迁移和侵袭,并促进细胞凋亡,其机制可能与抑制MAPK信号通路相关。

关键词: NFATc1, 肺腺癌, 分子机制

Abstract: Objective The aim of this study was to investigate the effects of NFATc1 expression on the proliferation,apoptosis,migration and invasion of lung adenocarcinoma NCI-H1299 cells,and its specific biological mechanisms. Methods Real time PCR was used to detect the relative levels of NFATc1 in three lung adenocarcinoma cell lines,and the NCI-H1299 cell line with stable knockdown of NFATc1 was constructed using lentivirus vectors.A MTT assay was used to detect the effect of NFATc1 on cell proliferation,the cell colony assay was used to detect the effect of NFATc1 on clone formation,the Transwell assay was used to detect the effect of NFATc1 on cell migration and invasion,and flow cytometry was used to detect the effect of NFATc1 on cell cycle and apoptosis.Western blot was used to detect the effects of NFATc1 on apoptosis,EMT-related proteins and MAPK signaling pathways protein expression. Results The expression of NFATc1 in lung adenocarcinoma NCI-H1299 cells was relatively high.Silencing NFATc1 expression could significantly inhibit cell proliferation(P＜0.05),clone formation(P＜0.05),migration(P＜0.05)and invasion(P＜0.05),the cell cycle arrested at the G1 phase(P＜0.05),and promote apoptosis(P＜0.05).The expression of Bax,cleaved caspase-3 and E-Cadherin protein increased(P＜0.05),and CDK4,c-Myc,ERK,p-ERK and N-Cadherin protein expression decreased(P＜0.05). Conclusion Inhibition of NFATc1 expression in human lung adenocarcinoma NCI-H1299 cells can significantly inhibit cell proliferation,arresting cell cycle,migration and invasion,and promote cell apoptosis.The mechanism may be related to the inhibition of MAPK signaling pathway.

Key words: NFATc1, Lung adenocarcinoma, Molecular mechanism

中图分类号:

R735.3

任凤海, 朱开彬, 王彦博, 周福成, 庞赛楠, 陈澜涛. NFATc1对人肺腺癌细胞增殖、凋亡和侵袭能力的影响[J]. 实用肿瘤学杂志, 2021, 35(5): 402-407.

REN Fenghai, ZHU Kaibin, WANG Yanbo, ZHOU Fucheng, PANG Sainan, CHEN Lantao. Effects of NFATc1 on the proliferation,apoptosis and invasion of human lung adenocarcinoma cells[J]. Journal of Practical Oncology, 2021, 35(5): 402-407.

0
/ / 推荐

导出引用管理器 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

链接本文: http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/10.11904/j.issn.1002-3070.2021.05.003

http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/Y2021/V35/I5/402

参考文献

1 Jauliac S,López-Rodriguez C,Shaw L,et al.The role of nfat transcription factors in integrin-mediated carcinoma invasion[J].Nature Cell Biology,2002,4(7):540-544.
2 Li L,Duan Z,Yu J,et al.Nfatc1 regulates cell proliferation,migration,and invasion of ovarian cancer skov3 cells in vitro and in vivo[J].Oncology Reports,2016,36(2):918-928.
3 Baumgart S,Chen N,Siveke J,et al.Inflammation-induced nfatc1-stat3 transcription complex promotes pancreatic cancer initiation by krasg12d[J].Cancer Discovery,2014,4(6):688-701.
4 Xu W,Gu J,Ren Q,et al.Nfatc1 promotes cell growth and tumorigenesis in ovarian cancer up-regulating c-myc through erk1/2/p38 mapk signal pathway[J].Tumour biology,2016,37(4):4493-4500.
5 文洪梅,陈杨,石青萍,等.2016年云南省肿瘤登记地区恶性肿瘤的发病和死亡分析[J].实用肿瘤学杂志 2020,34(6):485-490.
6 Miller KD,Nogueira L,Mariotto AB,et al. Cancer treatment and survivorship statistics,2019[J].CA Cancer J Clin,2019,69(5):363-385.
7 Herbst R,Morgensztern D,Boshoff C.The biology and management of non-small cell lung cancer[J].Nature,2018,553(7689):446-454.
8 Kawahara T,Kashiwagi E,Ide H,et al.The role of nfatc1 in prostate cancer progression:Cyclosporine a and tacrolimus inhibit cell proliferation,migration,and invasion[J].The Prostate,2015,75(6):573-584.
9 Buchholz M,Schatz A,Wagner M,et al.Overexpression of c-myc in pancreatic cancer caused by ectopic activation of nfatc1 and the ca2+/calcineurin signaling pathway[J].EMBO J,2006,25(15):3714-3724.
10 Oikawa T,Nakamura A,Onishi N,et al.Acquired expression of nfatc1 downregulates e-cadherin and promotes cancer cell invasion[J].Cancer Res,2013,73(16):5100-5109.
11 Kawahara T,Kashiwagi E,Li Y,et al.Cyclosporine a and tacrolimus inhibit urothelial tumorigenesis[J].Mol Carcinog,2016,55(2):161-169.
12 Kawahara T,Kashiwagi E,Ide H,et al.Cyclosporine a and tacrolimus inhibit bladder cancer growth through down-regulation of nfatc1[J].Oncotarget,2015,6(3):1582-1593.
13 Wang S,Kang X,Cao S,et al.Calcineurin/nfatc1 pathway contributes to cell proliferation in hepatocellular carcinoma[J].Dig Dis Sci,2012,57(12):3184-3188.
14 Iñiguez M,Martinez-Martinez S,Punzón C,et al.An essential role of the nuclear factor of activated t cells in the regulation of the expression of the cyclooxygenase-2 gene in human t lymphocytes[J].J Biol Chem,2000,275(31):23627-23635.
15 Liu Y,Liang T,Qiu X,et al.Down-regulation of nfatc1 suppresses proliferation,migration,invasion,and warburg effect in prostate cancer cells[J].Med Sci Monit,2019,25:1572-1581.
16 Sun Y,Liu WZ,Liu T,et al.Signaling pathway of mapk/erk in cell proliferation,differentiation,migration,senescence and apoptosis[J].J Recept Signal Transduct Res,2015,35(6):600-604.
17 Mondal A,Biswas R,Rhee YH,et al.Sulforaphene promotes bax/bcl2,mapk-dependent human gastric cancer ags cells apoptosis and inhibits migration via egfr,p-erk1/2 down-regulation[J].Gen Physiol Biophys,2016,35(1):25-34.
18 Lin H,Hao Y,Wan X,et al.Baicalein inhibits cell development,metastasis and emt and induces apoptosis by regulating erk signaling pathway in osteosarcoma[J].J Recept Signal Transduct Res,2020,40(1):49-57.
19 Yang J,Zhang JN,Chen WL,et al.Effects of aqp5 gene silencing on proliferation,migration and apoptosis of human glioma cells through regulating egfr/erk/p38 mapk signaling pathway[J].Oncotarget,2017,8(24):38444-38455.

[1]	王俊美, 潘慧卿, 李婧铱, 贾迪, 赵炜明, 吕昌莲. MT2-MMP在Ⅱ期肺腺癌中的表达及临床意义[J]. 实用肿瘤学杂志, 2021, 35(3): 243-247.
[2]	韩静, 蒲艳, 柳惠斌. SKA1对肾细胞癌细胞增殖凋亡的影响及其分子机制研究[J]. 实用肿瘤学杂志, 2020, 34(5): 404-411.
[3]	张孟哲, 康向东. Krüpple样转录因子4与结肠癌发生发展关系的研究进展[J]. 实用肿瘤学杂志, 2020, 34(5): 456-459.
[4]	陈澜涛, 颜巍, 刘静蕾, 姚磊. 防己诺林碱对肺癌H1299和A549细胞的作用及其分子机制研究[J]. 实用肿瘤学杂志, 2020, 34(2): 126-132.
[5]	刘光霞, 赵连春, 陈芳, 贾乾, 高伟, 侯瞻, 卢亚敏. ZCCHC12对甲状腺细胞恶性转化的影响与作用机制[J]. 实用肿瘤学杂志, 2020, 34(2): 133-138.
[6]	李亚飞, 张霄, 王雪飞, 翁明娇, 王天真. RNA结合蛋白Lin28在恶性肿瘤发生发展中的作用和分子机制[J]. 实用肿瘤学杂志, 2019, 33(5): 456-460.
[7]	马健力, 张明辉, 姬宏飞, 徐向英. PD-L1蛋白与CD8⁺TILs联合检测在可切除肺腺癌预后评估中的临床意义[J]. 实用肿瘤学杂志, 2019, 33(1): 40-46.
[8]	卞秀森, 李光, 关欣宇, 张伊, 狄畅, 马璨. UHRF1通过调控细胞自噬抑制肺腺癌细胞增殖的分子机制研究[J]. 实用肿瘤学杂志, 2018, 32(6): 498-502.
[9]	阚钧, 周岱翰综述, 张恩欣审校. 肿瘤合并心血管疾病的研究进展[J]. 实用肿瘤学杂志, 2018, 32(6): 558-561.
[10]	范宁宁, 耿敬姝. 长链非编码RNA MEG3在人胶质瘤细胞中的表达及作用研究[J]. 实用肿瘤学杂志, 2018, 32(3): 219-223.
[11]	袁萌,李晓莉. TRAP1与恶性肿瘤的关系及研究进展[J]. 实用肿瘤学杂志, 2017, 31(4): 371-375.
[12]	李志伟王凤云张倩倩李丁楠张纯慧燕飞虎张艳桥. STAT3通过上调Twist基因表达从而诱导肺腺癌细胞上皮-间质转化[J]. 实用肿瘤学杂志, 2014, 28(4): 310-314.
[13]	刘静蕾, 姜季, 张明岩, 王影, 刘永蕊, 王艳. 川芎嗪对人肺腺癌细胞株AGZY的增殖抑制及逆转耐药机制的研究[J]. 实用肿瘤学杂志, 2013, 27(4): 303-307.
[14]	姚志峰, 姚建新, 徐国平, 刘永彪. 西妥昔单抗对肺腺癌A549细胞株辐射增敏作用的研究[J]. 实用肿瘤学杂志, 2013, 27(1): 11-16.
[15]	张艳伟, 马晓欣. 新抑癌基因——TSLC1和DAL-1/4.1B与恶性肿瘤的关系[J]. 实用肿瘤学杂志, 2012, 26(6): 559-563.

NFATc1对人肺腺癌细胞增殖、凋亡和侵袭能力的影响

Effects of NFATc1 on the proliferation,apoptosis and invasion of human lung adenocarcinoma cells

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价