Oncotarget . 2015 Apr 20;6(11):8900-13. (IF:5.168).

本文采用的英格恩产品: RNA-Entranster-invivo

Macrophages promote benzopyrene-induced tumor transformation of human bronchial epithelial cells by activation of NF-κB and STAT3 signaling in a bionic airway chip culture and in animal models

Encheng Li  1 Zhiyun Xu  1 Hui Zhao  2 Zhao Sun  1 Lei Wang  3 Zhe Guo  1 Yang Zhao  1 Zhancheng Gao  4 Qi Wang  1

Affiliations

  • 1 Department of Respiratory Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
  • 2 Department of Physical Examination Center, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
  • 3 The Liaoning Provincial Key Laboratory for Micro/Nano Technology, Dalian University of Technology, Dalian, China.
  • 4 Department of Respiratory & Critical Care Medicine, The People’s Hospital of Peking University, Beijing, China.

Abstract

We investigated the role of macrophages in promoting benzopyrene (BaP)-induced malignant transformation of human bronchial epithelial cells using a BaP-induced tumor transformation model with a bionic airway chip in vitro and in animal models. The bionic airway chip culture data showed that macrophages promoted BaP-induced malignant transformation of human bronchial epithelial cells, which was mediated by nuclear factor (NF)-κB and STAT3 pathways to induce cell proliferation, colony formation in chip culture, and tumorigenicity in nude mice. Blockage of interleukin (IL)-6 or tumor necrosis factor (TNF)-α signaling or inhibition of NF-κB, STAT3, or cyclinD1 expression abrogated the effect of macrophages on malignant transformation in the bionic airway chip culture. In vivo, macrophages promoted lung tumorigenesis in a carcinogen-induced animal model. Similarly, blockage of NF-κB, STAT3, or cyclinD1 using siRNA transfection decreased the carcinogen-induced tumorigenesis in rats. We demonstrated that macrophages are critical in promoting lung tumorigenesis and that the macrophage-initiated TNF-α/NF-κB/cyclinD1 and IL-6/STAT3/cyclinD1 pathways are primarily responsible for promoting lung tumorigenesis.

Keywords: NF-κB; STAT3; macrophages; malignant transformation; microfluidic chip.

在线客服
在线客服
热线电话
 
0
    0
    我的购物车
    购物车是空的去下单