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Nicotine stimulates IL-8 expression via ROS/NF-κB and ROS/MAPK/AP-1 axis in human gastric cancer cells.
- Source :
-
Toxicology [Toxicology] 2022 Jan 30; Vol. 466, pp. 153062. Date of Electronic Publication: 2021 Dec 07. - Publication Year :
- 2022
-
Abstract
- Nicotine, a major alkaloid found in tobacco, is a significant risk factor for gastric cancer. IL-8, a pleiotropic cytokine, plays a vital role in cancer cell metastasis. The role of nicotine in IL-8 expression and the underlying mechanism is currently unknown. Here, we examined the effects of nicotine on IL-8 expression and explored the potential mechanisms in gastric cancer cells. We found that nicotine increases IL-8 expression. Specific inhibitor and mutagenesis studies showed that ROS and MAPK (Erk1/2, p38) were involved in this process. Deletion and site-directed mutagenesis studies indicate the involvement of transcription factor NF-κB and AP-1. ROS and ROS/MAPK (Erk1/2, p38) functioned as the upstream signaling molecules in the activation of NF-κB and AP-1, respectively. AGS gastric cancer cells pretreated with nicotine stimulate angiogenesis in the tumor microenvironment, partially abrogated by silencing IL-8 in AGS cells. In this study, we found that nicotine induces IL-8 expression via ROS/NF-κB and ROS/MAPK (Erk1/2, p38)/AP-1 axis in gastric cancer cells, thus stimulating endothelial cell proliferation and angiogenesis in the tumor microenvironment.<br /> (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Subjects :
- Cell Line, Tumor
Cell Proliferation drug effects
Humans
Mitogen-Activated Protein Kinases metabolism
NF-kappa B metabolism
Neovascularization, Pathologic
Reactive Oxygen Species metabolism
Transcription Factor AP-1 metabolism
Tumor Microenvironment drug effects
Endothelial Cells drug effects
Interleukin-8 metabolism
Nicotine pharmacology
Signal Transduction drug effects
Stomach Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3185
- Volume :
- 466
- Database :
- MEDLINE
- Journal :
- Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 34890707
- Full Text :
- https://doi.org/10.1016/j.tox.2021.153062