期刊
TOXICOLOGY
卷 466, 期 -, 页码 -出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2021.153062
关键词
nicotine; interleukin-8; gastric cancer; angiogenesis
资金
- Guangdong Basic and Applied Basic Research Foundation [2020A1515011433]
- Guangzhou Basic and Applied Basic Research Foundation [202102021052]
- Basic Science Research Program grant through the National Research Foundation of Korea - Ministry of Education, Science, and Technology [2018R1D1A1B07049918]
- Taishan Scholars Program of Shandong Province [tsqn201909147]
- Key Project at Central Government Level: the ability to establish the sustainable use of valuable Chinese medicine resources [2060302]
- National Research Foundation of Korea [2018R1D1A1B07049918] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
This study found that nicotine induces IL-8 expression via the ROS/NF-kappa B and ROS/MAPK (Erk1/2, p38)/AP-1 axis in gastric cancer cells, thus stimulating endothelial cell proliferation and angiogenesis in the tumor microenvironment.
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-kappa B and AP-1. ROS and ROS/MAPK (Erk1/2, p38) functioned as the upstream signaling molecules in the activation of NF-kappa B 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-kappa B and ROS/MAPK (Erk1/2, p38)/AP-1 axis in gastric cancer cells, thus stimulating endothelial cell proliferation and angiogenesis in the tumor microenvironment.
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