首都医科大学学报 ›› 2010, Vol. 31 ›› Issue (3): 329-334.

• 食管鳞癌的预防及早期诊断和干预 • 上一篇    下一篇

核因子KappaB途径在烟草提取物促食管鳞状细胞癌细胞增生中的作用

周巧直1, 陆三军2, 王星3, 朱圣韬1, 吕富靖1, 张澍田1*   

  1. 1. 首都医科大学附属北京友谊医院消化内科 北京市消化疾病中心;2. 河北省邯郸市第一医院病理科;3. 福建医科大学附属泉州第一医院传染病科
  • 收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2010-06-21 发布日期:2010-06-21
  • 通讯作者: 张澍田

Nuclear Factor-κB Signaling Pathway Constitutively Activated in Tobaccorelated Esophageal Squamous Cell Carcinoma

ZHOU Qiao-zhi1, LU San-jun2, WANG Xing3, ZHU Sheng-tao1, LV Fu-jing1, ZHANG Shu-tian1*   

  1. 1. Department of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing Digestive Disease Center;2. Department of Pathology, The First Hospital of HanDan, HeBei Province; 3. Department of Infectious Disease, The First Hospital of Quanzhou, FuJian Medical University, FuJian Province
  • Received:1900-01-01 Revised:1900-01-01 Online:2010-06-21 Published:2010-06-21
  • Contact: ZHANG Shu-tian

摘要: 目的 观察烟草乙醇提取物(ethanol extraction,EE)的促增生作用和核因子KappaB(nuclear factor of kappa B,NF-κB)抑制剂二硫氨基甲酸肽吡咯烷(pyrrolidine dithiocarbamate,PDTC)的抑制作用对NF-κB活性的影响,从而探讨NF-κB在烟草相关食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)发病机制中的作用。方法 EE分别与PDTC预处理的2株ESCC细胞共同孵育24 h后,用噻唑蓝法检测细胞增生情况;AnnexinV+PI双染检测细胞凋亡情况;凝胶迁移率、Western blotting方法检测干预前后EE对NF-κB活性的影响。采用免疫组织化学的方法测定ESCC组织标本中NF-κB的表达,并比较吸烟与非吸烟组阳性率的差异。结果 PDTC在25~200 mg/L浓度区间可抑制2株细胞的增生,呈剂量依赖性。EE作用24 h后,对2株细胞均呈现剂量依赖的促增生和抑制凋亡作用。EE 能促进2株细胞中NF-κB的活性。PDTC预处理后,EE的上述作用均减弱。ESCC组织中NFκB的阳性率为79.59 %;吸烟组NF-κB的阳性率高于非吸烟组。结论 EE可促进ESCC细胞株中NF-κB的活性,这种作用可被NF-κB抑制剂所阻断;ESCC组织中NF-κB呈高表达,吸烟可能增加ESCC组织中NF-κB的活性。

关键词: 食管鳞状细胞癌, 核因子KappaB, 吸烟

Abstract: Objective To investigate the influence of cigarette ethanol extraction(EE) and nuclear factor of kappa B(NF-κB) inhibitor, pyrrolidine dithiocarbamate(PDTC), on the constitutive NF-κB activity. Methods EE were incubated with two esophageal squamous cell carcinoma(ESCC) cell lines for 24 h respectively, which were pretreated with or without PDTC, proliferation rate was measured by MTT, apoptosis rate was measured by AnnexinV+PI, NF-κB activity by electrophoretic mobility shift assay(EMSA). Expression of NF-κB and the correlation between smoking were investigated in ESCC specimens from 49 cases by immunohistochemistry. Results PDTC(25~200 μg/ml) inhibited both ESCC cell lines proliferation in a dose-dependent manner. Cell proliferation was increased and cell apoptosis was inhibited by EE in a dose-dependent manner in both ESCC cell lines. EE could induce stimulation on NF-κB activity in both ESCC cell lines. The positive rate of NF-κB expression in specimens of human ESCC was 79.59%. The positive rate of NF-κB expression was higher for smokers compared to nonsmokers. Conclusion EE was shown to be a positive regulator of the activation of the NF-κB pathway in ESCC cell lines. PDTC, a specific inhibitor of NF-κB, can block the effect of EE. NF-κB is activated in ESCC tissue, cigarette smoking may be strongly associated with NF-κB activation.

Key words: esophageal squamous cell carcinoma, nuclear factor of kappa B, smoke

中图分类号: