FOXM1在食管鳞癌中的表达及对其放射敏感性的影响

刘琅嬛; 罗爱武; 陈科良; 谷蒙蒙; 肖倍倍; 邹士涛; 何超; 周俊东; 黄波

doi:10.11889/j.1000-3436.2016.rrj.34.060202

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FOXM1在食管鳞癌中的表达及对其放射敏感性的影响

辐射生物学与医学 | 更新时间：2021-12-10

- FOXM1在食管鳞癌中的表达及对其放射敏感性的影响
- Expression of FOXM1 and its effects on radiation sensitivity in esophageal squamous cell carcinoma (ESCC)
- 辐射研究与辐射工艺学报 2016年34卷第6期
- 作者机构：
  
  1.南华大学公共卫生学院衡阳 421001
  2.苏州大学放射医学与防护学院苏州 215123
  3.南京医科大学附属苏州市立医院南京 215001
- 作者简介：
  
  [ "刘琅嬛, 女, 1987年5月出生, 2010年6月毕业于湖南师范大学医学院, 现为南华大学在读硕士研究生, 研究方向为辐射防护剂研究, 医师", "LIU Langhuan (female) was born in May 1987 and graduated from Hunan Normal University Medical College in June 2010. Now she is a master candidate in University of South China majoring in radiation protection agent as a doctor" ]
  黄波, 博士, 副教授, E-mail:huangbo930@163.com PH.D. HUANG Bo, assosiate professer, E-mail:huangbo930@163.com
- 基金信息：
  
  湖南省自然科学基金项目(2016JJ2115);南华大学博士启动基金(2015XQD31);湖南省卫生计生委科研计划课题项目(C2015-17)
- DOI：10.11889/j.1000-3436.2016.rrj.34.060202
  中图分类号：
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刘琅嬛, 罗爱武, 陈科良, 等. FOXM1在食管鳞癌中的表达及对其放射敏感性的影响[J]. 辐射研究与辐射工艺学报, 2016,34(6):060202-8.

Langhuan LIU, Aiwu LUO, Keliang CHEN, et al. Expression of FOXM1 and its effects on radiation sensitivity in esophageal squamous cell carcinoma (ESCC)[J]. Journal of Radiation Research and Radiation Processing, 2016,34(6):060202-8.
刘琅嬛, 罗爱武, 陈科良, 等. FOXM1在食管鳞癌中的表达及对其放射敏感性的影响[J]. 辐射研究与辐射工艺学报, 2016,34(6):060202-8. DOI： 10.11889/j.1000-3436.2016.rrj.34.060202.

Langhuan LIU, Aiwu LUO, Keliang CHEN, et al. Expression of FOXM1 and its effects on radiation sensitivity in esophageal squamous cell carcinoma (ESCC)[J]. Journal of Radiation Research and Radiation Processing, 2016,34(6):060202-8. DOI： 10.11889/j.1000-3436.2016.rrj.34.060202.

摘要

采用Real-time PCR检测40例食管鳞状细胞癌及相对应癌旁组织中FOXM1（Forkhead box M1）mRNA表达情况；免疫组织化学方法检测94例食管鳞状细胞癌组织中FOXM1蛋白的表达情况，分析其与鳞状细胞癌临床病理之间的关系；采用针对FOXM1的siRNA沉默ECA-109、TE-1细胞中FOXM1基因表达水平，通过免疫荧光染色、克隆形成实验检测FOXM1对食管鳞状细胞癌放射敏感性的影响。结果表明，FOXM1 mRNA表达水平在食管癌组织中显著高于癌旁组织（,p,<, 0.01），其蛋白表达水平与病人生存期负相关。siRNA能有效干扰ECA-109细胞中的FOXM1表达水平，FOXM1沉默细胞中X-射线诱发的,γ,H2AX焦点显著多于对照细胞，FOXM1沉默细胞电离辐射后克隆形成能力显著低于对照细胞。结果提示，FOXM1在食管鳞癌中的表达增加，其表达水平与病人预后负相关；FOXM1基因沉默可显著增强细胞放射敏感性，因此，FOXM1有可能成为食管鳞癌的治疗靶点。

Abstract

Real-time PCR was used to examine the expression of FOXM1 (Forkhead box M1) in 40 esophageal squamous cell carcinoma (ESCC) tissues, and the adjacent normal tissues. Immunohistochemistry was used to examine the expression of FOXM1 protein in 94 ESCC tissues, and to analyze the relationship between ESCC and clinic pathologic. A small interfering RNA targeting FOXM1 was designed to silence the endogenous FOXM1 expression of ECA-109 and TE-1 cells. The effect of FOXM1 on radiation sensitive in esophageal squamous cell was observed by immunofluorescence stain, and colony formation assay. The results showed that FOXM1 mRNA expression level in esophageal cancer tissues was significantly higher than that of the adjacent tissues (,p,<, 0.01), and the protein level expression of it has negative correlation with the survival times; the designed siRNA could dramatically silence FOXM1 expression in ECA-109 cells; ,γ,H2AX focus induced by X-rays in FOXM1 silent cells was significantly higher than that in control cells; the clone formation ability of the silent FOXM1 group was significantly lower than that in the control group. The content of FOXM1 is improved in ESCC, and is negatively correlated with the prognosis of patients; the cell radiation sensitive proliferation is significantly improved in the silent FOXM1 ECA-109 cells. In conclusion, FOXM1 has the potential to be the treatment of esophageal squamous carcinoma target.

关键词

食管鳞癌FOXM1不良预后辐射敏感性DNA损伤修复

Keywords

Esophageal squamous cell carcinomaFOXM1 poor prognosisRadiation sensitivityDNA damage repair

references

A Jemal , R Siegel , E Ward , 等 . Cancer statistics, 2008 . CA-A Cancer Journal for Clinicians , 2008 . 58 (2 ):71 -96 . DOI:10.3322/CA.2007.0010http://doi.org/10.3322/CA.2007.0010 .

Z G Zhou , X S Gao , X Y Qiao , 等 . Literature analysis of radiotherapy for esophageal cancer in China . Chinese Journal of Cancer , 2010 . 29 (10 ):873 -881 . DOI:10.5732/cjc.010.10165http://doi.org/10.5732/cjc.010.10165.

M Katoh , M Katoh . Human FOX gene family (review) . International Journal of Oncology , 2004 . 25 (5 ):1495 -1500 . https://www.ncbi.nlm.nih.gov/pubmed/15492844https://www.ncbi.nlm.nih.gov/pubmed/15492844, .

M Alvarez-Fernandez , R H Medema . Novel functions of FoxM1: from molecular mechanisms to cancer therapy . Frontiers in Oncology , 2013 . 3 (30 ):1 -5 . DOI:10.3389/fonc.2013.00030http://doi.org/10.3389/fonc.2013.00030 .

M Halasi , A L Gartel . FOX (M1) news-it is cancer . Molecular Cancer Therapeutics , 2013 . 12 (3 ):245 -254 . DOI:10.1158/1535-7163.MCT-12-0712http://doi.org/10.1158/1535-7163.MCT-12-0712 .

I Wierstra . FOXM1 (Forkhead box M1) in tumorigenesis: overexpression in human cancer, implication in tumorigenesis, oncogenic functions, tumor-suppressive properties, and target of anticancer therapy . Advances in Cancer Research , 2013 . 119 191 -419 . DOI:10.1016/B978-0-12-407190-2.00016-2http://doi.org/10.1016/B978-0-12-407190-2.00016-2 .

D K Yang , C H Son , S K Lee , 等 . Forkhead box M1 expression in pulmonary squamous cell carcinoma: correlation with clinicopathologic features and its prognostic significance . Human Pathology , 2009 . 40 (4 ):464 -470 . DOI:10.1016/j.humpath.2008.10.001http://doi.org/10.1016/j.humpath.2008.10.001 .

G Yu , A Zhou , J Xue , 等 . FoxM1 promotes breast tumorigenesis by activating PDGF-A and forming a positive feedback loop with the PDGF/AKT signaling pathway . Oncotarget , 2015 . 6 (13 ):11281 -11294 . DOI:10.18632/oncotarget.3596http://doi.org/10.18632/oncotarget.3596 .

L Xia , W Huang , D Tian , 等 . Upregulated FoxM1 expression induced by hepatitis B virus X protein promotes tumor metastasis and indicates poor prognosis in hepatitis B virus-related hepatocellular carcinoma . Journal of Hepatology , 2012 . 57 (3 ):600 -612 . DOI:10.1016/j.jhep.2012.04.020http://doi.org/10.1016/j.jhep.2012.04.020 .

Y Tan , P Raychaudhuri , R H Costa . Chk2 mediates stabilization of the FoxM1 transcription factor to stimulate expression of DNA repair genes . Molecular and Cellular Biology , 2007 . 27 (3 ):1007 -1016 . DOI:10.1128/MCB.01068-06http://doi.org/10.1128/MCB.01068-06 .

L Myllynen , T Rieckmann , J Dahm-Daphi , 等 . In tumor cells regulation of DNA double strand break repair through EGF receptor involves both NHEJ and HR and is independent of p53 and K-Ras status . Radiotherapy and Oncology , 2011 . 101 (1 ):147 -151 . DOI:10.1016/j.radonc.2011.05.046http://doi.org/10.1016/j.radonc.2011.05.046 .

L J Monteiro , P Khongkow , M Kongsema , 等 . The Forkhead Box M1 protein regulates BRIP1 expression and DNA damage repair in epirubicin treatment . Oncogene , 2013 . 32 (39 ):4634 -4645 . DOI:10.1038/onc.2012.491http://doi.org/10.1038/onc.2012.491 .

N Zhang , X Wu , L Yang , 等 . FoxM1 inhibition sensitizes resistant glioblastoma cells to temozolomide by downregulating the expression of DNA-repair gene Rad51 . Clinical Cancer Research , 2012 . 18 (21 ):5961 -5971 . DOI:10.1158/1078-0432.CCR-12-0039http://doi.org/10.1158/1078-0432.CCR-12-0039 .

X L Li , Q H Meng , S J Fan . Adenovirus-mediated expression of UHRF1 reduces the radiosensitivity of cervical cancer HeLa cells to gamma-irradiation . Acta Pharmacologica Sinica , 2009 . 30 (4 ):458 -466 . DOI:10.1038/aps.2009.18http://doi.org/10.1038/aps.2009.18 .

J M Kwok , B Peck , L J Monteiro , 等 . FOXM1 confers acquired cisplatin resistance in breast cancer cells . Molecular Cancer Research: MCR , 2010 . 8 (1 ):24 -34 . DOI:10.1158/1541-7786.MCR-09-0432http://doi.org/10.1158/1541-7786.MCR-09-0432 .

闫海霞 , 符国胜 . 术前放疗对食管癌患者影响的临床分析 . 当代医学 , 2011 . 17 (16 ):21 -22 . DOI:10.3969/j.issn.1009-4393.2011.16.014http://doi.org/10.3969/j.issn.1009-4393.2011.16.014 .

Haixia YAN , Guosheng FU . The clinical analysis of preoperative radiotherapy Influence for esophageal cancer patients . Contemporary Medicine , 2011 . 17 (16 ):21 -22 . DOI:10.3969/j.issn.1009-4393.2011.16.014http://doi.org/10.3969/j.issn.1009-4393.2011.16.014 .

武莉萍 , 杨留勤 . 食管癌根治术后放射治疗的价值 . 陕西肿瘤医学 , 2002 . 10 (3 ):189 -190 . http://www.cnki.com.cn/Article/CJFDTOTAL-SXZL200203018.htmhttp://www.cnki.com.cn/Article/CJFDTOTAL-SXZL200203018.htm, .

Liping WU , Liuqin YANG . Postoperative radiotherapy after radical resection for esophageal carcinoma . Shaanxi Oncology Medicine , 2002 . 10 (3 ):189 -190 . http://www.cnki.com.cn/Article/CJFDTOTAL-SXZL200203018.htmhttp://www.cnki.com.cn/Article/CJFDTOTAL-SXZL200203018.htm, .

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