倪猛,殷涛,李明,杨峥,刘驰,樊宏伟.程序性细胞死亡4基因增强胰腺癌细胞放射敏感性的研究[J].中华放射医学与防护杂志,2017,37(11):810-815
程序性细胞死亡4基因增强胰腺癌细胞放射敏感性的研究
Programmed cell death 4 enhances radiosensitivity of pancreatic cancer cells
投稿时间:2017-04-07  修订日期:2017-04-07
DOI:10.3760/cma.j.issn.0254-5098.2017.11.002
中文关键词:  胰腺癌  放射敏感性  程序性细胞死亡4  β-连环蛋白  c-myc
英文关键词:Pancreatic cancer  Radiosensitivity  Programmed cell death 4  β-catenin  c-myc
基金项目:国家自然科学基金(81372665)
作者单位E-mail
倪猛 473000 南阳, 郑州大学附属南阳医院 南阳市中心医院消化内科  
殷涛 430022 武汉, 华中科技大学同济医学院附属协和医院胰腺外科  
李明 473000 南阳, 郑州大学附属南阳医院 南阳市中心医院肿瘤内科  
杨峥 473000 南阳, 郑州大学附属南阳医院 南阳市中心医院放疗科  
刘驰 473000 南阳, 郑州大学附属南阳医院 南阳市中心医院肝脏外科  
樊宏伟 473000 南阳, 郑州大学附属南阳医院 南阳市中心医院消化内科 xhnkfhw@sohu.com 
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中文摘要:
      目的 探讨程序性细胞死亡4(PDCD4)对胰腺癌细胞放疗敏感性的影响及机制。方法 收集胰腺癌组织及对应的癌旁组织,采用RT-PCR和Western blot检测PDCD4表达水平。以人胰腺癌细胞Sw1990为研究对象,细胞转染PDCD4过表达载体(pIRES2-PDCD4组)、空载体(pIRES2组),同时以只加入转染试剂的细胞为未转染组,RT-PCR和Western blot检测PDCD4表达水平。细胞经放射处理后,流式细胞术检测细胞凋亡情况,细胞克隆实验检测细胞放射敏感性,Western blot检测细胞中β-连环蛋白、Wnt信号通路下游靶基因c-myc、活化的含半胱氨酸的天冬氨酸蛋白水解酶3(Cleaved Caspase-3)表达水平。结果 胰腺癌组织中PDCD4 mRNA和蛋白表达水平均明显低于癌旁组织(t=4.869、9.208,P<0.05)。pIRES2-PDCD4组细胞中PDCD4 mRNA和蛋白表达水平均明显高于未转染组(t=9.074、18.927,P<0.05)。照射处理后,pIRES2-PDCD4组细胞凋亡率及细胞中Cleaved Caspase-3水平均明显高于未转染组(t=3.670、4.086,P<0.05),而细胞中β-连环蛋白、c-myc表达水平均明显低于未转染组(t=9.242、17.644,P<0.05)。pIRES2-PDCD4组放射敏感性高于未转染组,增敏比为1.843。结论 PDCD4能够增加胰腺癌细胞放射敏感性,促进胰腺癌细胞凋亡,作用机制可能与Wnt信号通路有关。
英文摘要:
      Objective To investigate the effect and mechanism of programmed cell death 4 (PDCD4) on radiosensitivity of pancreatic cancer cells. Methods Pancreatic cancer tissues and corresponding adjacent tissues were collected, the expression level of PDCD4 was detected by RT-PCR and Western blot. Human pancreatic cancer cells Sw1990 were transfected with PDCD4 overexpression vector (group pIRES2-PDCD4), empty vector (pIRES2 group), and treated with transfection reagent, respectively. The expression level of PDCD4 was detected by RT-PCR and Western blot. After radiation treatment, cell apoptosis was detected by flow cytometry, cell survival was detected by clone assay, and the expression levels of β-catenin, c-myc and Cleaved Caspase-3 were detected by Western blot. Results The expression of PDCD4 mRNA and protein in pancreatic cancer tissues was significantly lower than that in adjacent tissues (t=4.869, 9.208, P<0.05). The expression of PDCD4 mRNA and protein in pIRES2-PDCD4 group was significantly lower than that in the non-transfection group (t=9.074, 18.927, P<0.05). After radiation, the apoptosis rate and Cleaved Caspase-3 level in the pIRES2-PDCD4 group were significantly higher than those in the non-transfection group (t=3.670, 4.086, P<0.05), while the expression levels of β-catenin and c-myc in the cells were significantly lower than those in the non-transfection group (t=9.242, 17.644, P<0.05). The radiosensitivity of pIRES2-PDCD4 group was higher than that of non-transfection group, and the sensitization ratio was 1.843. Conclusions PDCD4 can increase radiosensitivity and promote apoptosis of pancreatic cancer cells, to which the Wnt signaling pathway may be related.
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