高级搜索

NF-κB与放射线诱导的人食管癌细胞上皮间质转化的关系

杨晔, 薛晓英, 冉玉格, 周欢娣, 张歌, 肖志清, 刘军领

杨晔, 薛晓英, 冉玉格, 周欢娣, 张歌, 肖志清, 刘军领. NF-κB与放射线诱导的人食管癌细胞上皮间质转化的关系[J]. 肿瘤防治研究, 2016, 43(11): 921-925. DOI: 10.3971/j.issn.1000-8578.2016.11.001
引用本文: 杨晔, 薛晓英, 冉玉格, 周欢娣, 张歌, 肖志清, 刘军领. NF-κB与放射线诱导的人食管癌细胞上皮间质转化的关系[J]. 肿瘤防治研究, 2016, 43(11): 921-925. DOI: 10.3971/j.issn.1000-8578.2016.11.001
YANG Ye, XUE Xiaoying, RAN Yuge, ZHOU Huandi, ZHANG Ge, XIAO Zhiqing, LIU Junling. Relationship Between NF-κB and Epithelial-to-mesenchymal Transition of Radiation-induced Human Esophageal Carcinoma Cells[J]. Cancer Research on Prevention and Treatment, 2016, 43(11): 921-925. DOI: 10.3971/j.issn.1000-8578.2016.11.001
Citation: YANG Ye, XUE Xiaoying, RAN Yuge, ZHOU Huandi, ZHANG Ge, XIAO Zhiqing, LIU Junling. Relationship Between NF-κB and Epithelial-to-mesenchymal Transition of Radiation-induced Human Esophageal Carcinoma Cells[J]. Cancer Research on Prevention and Treatment, 2016, 43(11): 921-925. DOI: 10.3971/j.issn.1000-8578.2016.11.001

NF-κB与放射线诱导的人食管癌细胞上皮间质转化的关系

基金项目: 

河北省自然科学基金 C2009001151

河北医科大学第二医院院基金 2h2201505

详细信息
    作者简介:

    杨晔(1986-),女,硕士,医师,主要从事肿瘤放化疗的基础及临床研究

    通讯作者:

    薛晓英,E-mail: xxy6412@163.com

  • 中图分类号: R735.1

Relationship Between NF-κB and Epithelial-to-mesenchymal Transition of Radiation-induced Human Esophageal Carcinoma Cells

More Information
  • 摘要:
    目的 

    探讨NF-κB与放射线诱导的人食管癌细胞上皮间质转化(EMT)间的关系。

    方法 

    累积照射食管癌Eca109细胞60 Gy,得到Eca109R60细胞,克隆形成实验检测其放射抵抗性,显微镜下观察细胞形态学变化。Real-time PCR和免疫细胞化学检测Eca109和Eca109R60细胞NF-κB、E-cadherin和Vimentin的表达情况。

    结果 

    Eca109R60细胞具备了EMT样表型且放射抵抗性更强。Eca109R60细胞中E-cadherin mRNA表达明显下调(P=0.003),Vimentin、NF-κB mRNA表达升高(P=0.004,P=0.004)。相关性分析显示NF-κB与E-cadherin mRNA表达呈负相关,与Vimentin未见有明显相关性,但已显示出正相关的趋势。免疫细胞化学法检测Eca109R60细胞E-cadherin阳性染色程度明显减弱,Vimentin、NF-κB p65阳性染色程度明显增强。

    结论 

    Eca109R60细胞放射抗性可能由EMT与NF-κB信号通路相互作用调控。

     

    Abstract:
    Objective 

    To explore the relationship between NF-κB and epithelial-to-mesenchymal transition (EMT) of human esophageal carcinoma cells induced by the radiation.

    Methods 

    We irradiated cumulatively human esophageal carcinoma cells Eca109 with 60Gy to get Eca109R60 cells. The radio-resistance was detected by means of a standard colony-formation assay. Cells morphological change was observed under microscope. Meanwhile,Real-time PCR and immunocytochemistry were used to detect the expression level of NF-κB,E-cadherin and Vimentin in esophageal epithelial cell lines Eca109 and Eca109R60,respectively.

    Results 

    Eca109R60 cells had EMT-like phenotype and stronger irradiation resistance(IR). In Eca109R60 cells,the expression level of E-cadherin mRNA was significantly down-regulated (P=0.003) . There were significant upregulation in the expression levels of Vimentin and NF-κB mRNA (P=0.004,P=0.004) . It showed a negative correlation between NF-κB and E-cadherin by the correlation analysis. There was not an evident correlation between NF-κB and Vimentin,but a trend to negative correlation. From the result of immunocytochemistry staining,a weaker expression of E-cadherin protein while stronger expression of Vimentin and NF-κB p65 protein were found.

    Conclusion 

    The radio-resistance of human esophageal carcinoma cells Eca109R60 may be regulated through the interaction between EMT and NF-κB signaling pathway.

     

  • 图  1   Eca109与Eca109R60细胞的形态观察

    Figure  1   Morphology of Eca109 and Eca109R60 cells

    图  2   Eca109与Eca109R60细胞放射抵抗性的比较

    Figure  2   Comparison of radio-resistance between Eca109 and Eca109R60 cells

    图  3   Eca109与Eca109R60细胞中E-cadherin mRNA、Vimentin mRNA及NF-κB mRNA的表达

    Figure  3   Expression of E-cadherin mRNA,Vimentin mRNA and NF-κB mRNA in Eca109 and Eca109R60 cells

    图  4   Eca109与Eca109R60细胞中E-cadherin、Vimentin及NF-κBp65蛋白的表达 (×400)

    Figure  4   Expression of E-cadherin,Vimentin and NF-κBp65 protein in Eca109 and Eca109R60 cells(×400)

    表  1   Eca109与Eca109R60放射生物学参数

    Table  1   Radiation biology parameter of Eca109 and Eca109R60 cells

    下载: 导出CSV
  • [1]

    Stewart BW,Wild C. World Cancer Report 2014[M]. Lyon:The International Agency for Research on Cancer,2014: 529-30.

    [1] Stewart BW, Wild C. World Cancer Report 2014[M]. Lyon:The International Agency for Research on Cancer, 2014: 529-30.
    [2] Theys J, Jutten B, Habets R, et al. E-cadherin loss associated with EMT promotes radioresistance in human tumor cells[J]. Radiother Oncol, 2011, 99(3): 392-7.
    [2]

    Theys J,Jutten B,Habets R,et al. E-cadherin loss associated with EMT promotes radioresistance in human tumor cells[J]. Radiother Oncol,2011,99(3): 392-7. doi: 10.1016/j.radonc.2011.05.044

    [3]

    Lan F,Yue X,Ren G,et al. miR-15a/16 enhances radiation sensitivity of non-small cell lung cancer cells by targeting the TLR1/NF-κB signaling pathway[J]. Int J Radiat Oncol Biol Phys,2015,91(1): 73-81. doi: 10.1016/j.ijrobp.2014.09.021

    [3] Lan F, Yue X, Ren G, et al. miR-15a/16 enhances radiation sensitivity of non-small cell lung cancer cells by targeting the TLR1/NF-κB signaling pathway[J]. Int J Radiat Oncol Biol Phys, 2015, 91(1): 73-81.
    [4] Zhang Y, Wei Y, Zhu Z, et al. Icariin enhances radiosensitivity of colorectal cancer cells by suppressing NF-κB activity[J]. Cell Biochem Biophys, 2014, 69(2): 303-10.
    [4]

    Zhang Y,Wei Y,Zhu Z,et al. Icariin enhances radiosensitivity of colorectal cancer cells by suppressing NF-κB activity[J]. Cell Biochem Biophys,2014,69(2): 303-10. doi: 10.1007/s12013-013-9799-x

    [5] Ahmed KM, Zhang H, Park CC. NF-κB regulates radioresistance mediated by β1-integrin in three-dimensional culture of breast cancer cells[J]. Cancer Res, 2013, 73(12): 3737-48.
    [5]

    Ahmed KM,Zhang H,Park CC. NF-κB regulates radioresistance mediated by β1-integrin in three-dimensional culture of breast cancer cells[J]. Cancer Res,2013,73(12): 3737-48. doi: 10.1158/0008-5472.CAN-12-3537

    [6] 阴骏,李涛. 食管癌个体化综合治疗的研究[J]. 国际肿瘤学杂志,2012,39(7): 526-9.

    Yin J,Li T. Individual comprehensive therapy study for esophageal carinoma[J]. Guo Ji Zhong Liu Xue Za Zhi,2012,39(7): 526-9.in J,Li T. Individual comprehensive therapy study for esophageal carinoma[J]. Guo Ji Zhong Liu Xue Za Zhi,2012,39(7): 526-9.

    [6] 阴骏, 李涛. 食管癌个体化综合治疗的研究[J]. 国际肿瘤学杂 志, 2012, 39(7): 526-9. [Yin J, Li T. Individual comprehensive therapy study for esophageal carinoma[J]. Guo Ji Zhong Liu Xue Za Zhi, 2012, 39(7): 526-9.]
    [7]

    Che SM,Zhang XZ,Liu XL,et al. The radiosensitization effect of NS398 on esophageal cancer stem cell-like radioresistant cells[J]. Dis Esophagus,2011,24(4): 265-73. doi: 10.1111/j.1442-2050.2010.01138.x

    [7] Che SM, Zhang XZ, Liu XL, et al. The radiosensitization effect of NS398 on esophageal cancer stem cell-like radioresistant cells[J]. Dis Esophagus, 2011, 24(4): 265-73.
    [8] 李文雯, 张琳丽, 胡国清. 转录因子Snail对食管癌Eca-109细胞 侵袭和迁移的影响[J]. 肿瘤防治研究, 2015, 42(4): 319-23. [Li WW, Zhang LL, Hu GQ. Effect of transcription factor snail on invasion and migration of esophageal carcinoma cell line Eca- 109[J]. Zhong Liu Fang Zhi Yan Jiu, 2015, 42(4): 319-23.]
    [8] 李文雯,张琳丽,胡国清. 转录因子Snail对食管癌Eca-109细胞侵袭和迁移的影响[J]. 肿瘤防治研究,2015,42(4): 319-23. http://www.zlfzyj.com/CN/abstract/abstract8457.shtml

    Li WW,Zhang LL,Hu GQ. Effect of transcription factor snail on invasion and migration of esophageal carcinoma cell line Eca-109[J]. Zhong Liu Fang Zhi Yan Jiu,2015,42(4): 319-23.i WW,Zhang LL,Hu GQ. Effect of transcription factor snail on invasion and migration of esophageal carcinoma cell line Eca-109[J]. Zhong Liu Fang Zhi Yan Jiu,2015,42(4): 319-23. http://www.zlfzyj.com/CN/abstract/abstract8457.shtml

    [9]

    Tsukamoto H,Shibata K,Kajiyama H,et al. Irradiation-induced epithelial-mesenchymal transition (EMT) related to invasive potential in endometrial carcinoma cells[J]. Gynecol Oncol,2007,107(3): 500-4. doi: 10.1016/j.ygyno.2007.08.058

    [9] Tsukamoto H, Shibata K, Kajiyama H, et al. Irradiation-induced epithelial-mesenchymal transition (EMT) related to invasive potential in endometrial carcinoma cells[J]. Gynecol Oncol, 2007, 107(3): 500-4.
    [10] Su H, Jin X, Shen L, et al. Inhibition of cyclin D1 enhances sensitivity to radiotherapy and reverses epithelial to mesenchymal transition for esophageal cancer cells[J]. Tumour Biol, 2016, 37(4): 5355-63.
    [10]

    Su H,Jin X,Shen L,et al. Inhibition of cyclin D1 enhances sensitivity to radiotherapy and reverses epithelial to mesenchymal transition for esophageal cancer cells[J]. Tumour Biol,2016,37(4): 5355-63. doi: 10.1007/s13277-015-4393-z

    [11]

    Meyn RE,Milas L,Ang KK. The role of apoptosis in radiation oncology[J]. Int J Radiat Biol,2009,85(2): 107-15. doi: 10.1080/09553000802662595

    [11] Meyn RE, Milas L, Ang KK. The role of apoptosis in radiation oncology[J]. Int J Radiat Biol, 2009, 85(2): 107-15.
    [12] Bhat KP, Balasubramaniyan V, Vaillant B, et al. Mesenchymal differentiation mediated by NF-κB promotes radiation resistance in glioblastoma[J]. Cancer Cell, 2013, 24(3): 331-46.
    [12]

    Bhat KP,Balasubramaniyan V,Vaillant B,et al. Mesenchymal differentiation mediated by NF-κB promotes radiation resistance in glioblastoma[J]. Cancer Cell,2013,24(3): 331-46. doi: 10.1016/j.ccr.2013.08.001

    [13]

    Xue XY,Liu ZH,Jing FM,et al. Relationship between NRAGE and the radioresistance of esophageal carcinoma cell line TE13R120[J]. Chin J Cancer,2010,29(10): 900-6. doi: 10.5732/cjc.010.10141

    [13] Xue XY, Liu ZH, Jing FM, et al. Relationship between NRAGE and the radioresistance of esophageal carcinoma cell line TE13R120[J]. Chin J Cancer, 2010, 29(10): 900-6.
    [14]

    Duru N,Candas D,Jiang G,et al. Breast cancer adaptive resistance: HER2 and cancer stem cell repopulation in a heterogeneous tumor society[J]. J Cancer Res Clin Oncol,2014,140(1):1-14. doi: 10.1007/s00432-013-1494-1

    [14] Duru N, Candas D, Jiang G, et al. Breast cancer adaptive resistance: HER2 and cancer stem cell repopulation in a heterogeneous tumor society[J]. J Cancer Res Clin Oncol, 2014, 140(1):1-14.
    [15] Sinha S, Ghildiyal R, Mehta VS, et al. ATM-NFκB axis-driven TIGAR regulates sensitivity of glioma cells to radiomimetics in the presence of TNFα[J]. Cell Death Dis, 2013, 4: e615.
    [15]

    Sinha S,Ghildiyal R,Mehta VS,et al. ATM-NFκB axis-driven TIGAR regulates sensitivity of glioma cells to radiomimetics in the presence of TNFα[J]. Cell Death Dis,2013,4: e615. doi: 10.1038/cddis.2013.128

    [16] Sun Q, Yao X, Ning Y, et al. Overexpression of response gene to complement 32(RGC32) promotes cell invasion and induces epithelial-mesenchymal transition in lung cancer cells via the NF- κB signaling pathway[J]. Tumour Biol, 2013, 34(5): 2995-3002.
    [16]

    Sun Q,Yao X,Ning Y,et al. Overexpression of response gene to complement 32(RGC32) promotes cell invasion and induces epithelial-mesenchymal transition in lung cancer cells via the NF-κB signaling pathway[J]. Tumour Biol,2013,34(5): 2995-3002. doi: 10.1007/s13277-013-0864-2

    [17] Huber MA, Azoitei N, Baumann B, et al. NF-kappaB is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression[J]. J Clin Invest, 2004, 114(4): 569-81.
    [17]

    Huber MA,Azoitei N,Baumann B,et al. NF-kappaB is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression[J]. J Clin Invest,2004,114(4): 569-81. doi: 10.1172/JCI200421358

    [18] 石磊,王世明,贺杰峰. 核转录因子-κB在胰腺癌中的表达及其与上皮细胞间质转化的关系[J]. 肿瘤研究与临床,2011,23(3): 191-3. http://cdmd.cnki.com.cn/Article/CDMD-10114-1011092173.htm

    Shi L,Wang SM,He JF. Expression of NF-κB and its relation with epithelial-mesenchymal transition in pancreatic cancer[J]. Zhong Liu Yan Jiu Yu Lin Chuang,2011,23(3): 191-3.hi L,Wang SM,He JF. Expression of NF-κB and its relation with epithelial-mesenchymal transition in pancreatic cancer[J]. Zhong Liu Yan Jiu Yu Lin Chuang,2011,23(3): 191-3. http://cdmd.cnki.com.cn/Article/CDMD-10114-1011092173.htm

    [18] 石磊, 王世明, 贺杰峰. 核转录因子-Κ B在胰腺癌中的表达 及其与上皮细胞间质转化的关系[J]. 肿瘤研究与临床, 2011, 23(3): 191-3. [Shi L, Wang SM, He JF. Expression of NF-κB and its relation with epithelial-mesenchymal transition in pancreatic cancer[J]. Zhong Liu Yan Jiu Yu Lin Chuang, 2011, 23(3): 191-3.]
    [19]

    Yan Z,Yin H,Wang R,et al. Overexpression of integrin-linked kinase (ILK) promotes migration and invasion of colorectal cancer cells by inducing epithelial-mesenchymal transition via NF-κB signaling[J]. Acta Histochem,2014,116(3): 527-33. doi: 10.1016/j.acthis.2013.11.001

    [19] Yan Z, Yin H, Wang R, et al. Overexpression of integrin-linked kinase (ILK) promotes migration and invasion of colorectal cancer cells by inducing epithelial-mesenchymal transition via NF-κB signaling[J]. Acta Histochem, 2014, 116(3): 527-33.
图(4)  /  表(1)
计量
  • 文章访问数:  1430
  • HTML全文浏览量:  308
  • PDF下载量:  339
  • 被引次数: 0
出版历程
  • 收稿日期:  2015-12-07
  • 修回日期:  2016-03-13
  • 网络出版日期:  2024-02-04
  • 刊出日期:  2016-10-31

目录

    /

    返回文章
    返回
    x 关闭 永久关闭