Role of IKBKE in malignant transformation of human bronchial epithelial cells induced by cigarette smoke condensates

Jihong ZHOU; Lei HONG; Peng JIANG; Nana YUAN; Qin LI; Yuqing CHEN; Xiaojing WANG; Maoxiang ZHU; Zhihua YANG; Wei LI

doi:10.16016/j.1000-5404.201804105

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Role of IKBKE in malignant transformation of human bronchial epithelial cells induced by cigarette smoke condensates

Basic Medicine | 更新时间：2026-01-09

- Role of IKBKE in malignant transformation of human bronchial epithelial cells induced by cigarette smoke condensates
- Journal of Third Military Medical University Vol. 40, Issue 13, Pages: 1221-1228(2018)
- 作者机构：
  
  1.233002 安徽蚌埠，蚌埠医学院生物化学与分子生物学教研室
  2.233004 安徽蚌埠，蚌埠医学院第一附属医院呼吸与危重症医学科，安徽省呼吸系病临床基础重点实验室
  3.100850 北京，军事医学科学院放射与辐射研究所
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81172213);the General Program of Natural Science Foundation of Anhui Province(1408085MH14);the Key Project of Natural Science Foundation of Higher Education of Anhui Provincial Educational Committee(KJ2016A487)
- DOI：10.16016/j.1000-5404.201804105
  CLC： R122.07;R730.23;R734.1
- Received：16 April 2018，
  
  Revised：2018-05-04，
  
  Published：15 July 2018
- 稿件说明：
移动端阅览
Jihong ZHOU, Lei HONG, Peng JIANG, et al. Role of IKBKE in malignant transformation of human bronchial epithelial cells induced by cigarette smoke condensates[J]. Journal of Third Military Medical University, 2018, 40(13): 1221-1228.
DOI：

Jihong ZHOU, Lei HONG, Peng JIANG, et al. Role of IKBKE in malignant transformation of human bronchial epithelial cells induced by cigarette smoke condensates[J]. Journal of Third Military Medical University, 2018, 40(13): 1221-1228. DOI： 10.16016/j.1000-5404.201804105.

摘要

目的

探讨核因子κB抑制蛋白E抗体(inhibitor of nuclear factor kappa-B kinase subunit epsilon，IKBKE)在卷烟烟气凝集物(cigarette smoke condensate，CSC)诱导永生化人支气管上皮细胞BEP2D恶性转化中的作用及其分子机制。

方法

CSC慢性染毒BEP2D细胞至P70代(0.001支烟/mL)，裸鼠皮下成瘤实验观察染毒细胞是否发生恶性转化；采用Western blot检测各代细胞以及CSC急性染毒BEP2D细胞(0.006支烟/mL)4、8、12、24 h和48 h后IKEBE的表达；免疫组化检测烟熏1、3、9个月A/J小鼠外周小气道和瘤体组织IKBKE的表达；慢病毒IKBKE-siRNA感染P70细胞，观察其对细胞增殖、细胞克隆形成和凋亡的影响；观察敲减IKBKE对STAT3信号通路分子表达的影响及STAT3信号通路激活剂IL-6对细胞恶性转化的影响。

结果

与P0、P50细胞相比，P70细胞具有恶性转化表型；IKBKE显著高表达于P70细胞(

＜0.05)，亦是CSC诱导的早期分子事件；在烟气暴露A/J小鼠肺肿瘤组织中IKBKE表达显著

增高(

＜0.01)；siRNA沉默IKBKE可显著抑制细胞增殖和细胞克隆形成，诱导细胞凋亡；该作用与抑制STAT3磷酸化有关。

结论

IKBKE可能通过调控STAT3通路抑制细胞凋亡，促进其增殖，参与吸烟诱导肺癌发生。

Abstract

Objective

To investigate the role and molecular mechanism of inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE) in the malignant transformation of immortalized human bronchial epithelial cell line BEP2D induced by cigarette smoke condensate (CSC).

Methods

CSC (0.001 cigarette/mL) was used to infect BEP2D cells chronically and the cells were passed to P70. The subcutaneous tumorigenesis test in nude mice was used to observe whether malignant transformation occurred in the cultured cells. Western blotting was used to detect the expression of IKBKE

in each generation of chronically infected cells

and in acutely induced cells in 4

and 48 h after exposure to CSC (0.006 cigarettes/mL). Immunohistochemical assay was used to detect the IKBEK expression in peripheral small airways and tumor tissue of A/J mice after smoking for 1

3 and 9 months. After the P70 cells were infected with lentiviral vector IKBKE-siRNA

its effects on cell proliferation

cell clone formation and apoptosis were observed. The effects of IKBKE knockdown on STAT3 signaling pathway and the effect of STAT3 signaling pathway activator interleukin 6 (IL-6) on malignant transformation of cells were investigated.

Results

Compared with P0 and P50 cells

P70 cells showed malignant transformation phenotype. IKBKE was highly expressed in the P70 cells

which was also an early molecular event induced by CSC. In the A/J mice exposed to smoke

IKBKE expression was significantly increased in the lung cancer tissues. Silencing of IKBKE by siRNA significantly inhibited cell proliferation and cell colony formation

and induced cell apoptosis. And this effect was related to the inhibition of STAT3 pathway.

Conclusion

IKBKE may inhibit cell apoptosis

promote cell proliferation and participate in smoking-induced lung cancer by regulating the STAT3 pathway.

关键词

Keywords

references

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