Effects of the NF-κB Pathway Agonist IL-1β on Non-Small Cell Lung Cancer Cell Lines.

Abstract

OBJECTIVE:

Canakinumab is an interleukin (IL)-1β inhibitory antibody. Recently, a large trial of canakinumab in cardiac patients described lower lung cancer incidence in patients treated with canakinumab compared to controls. This finding is the basis for ongoing clinical trials of canakinumab in lung cancer. To address the underlying mechanism, we established lung cancer co-cultures to investigate the interactions between lung cancer cells and immunocyte macrophages as related to the expression of IL-1β and the effect of IL-1β on the NF-κB pathway on lung cancer cells.

METHODS:

Lung cancer cell lines H838 and H1975 and macrophages were mono-cultured separately as control groups. Lung cancer cell lines and macrophages were co-cultured respectively in a ratio of 5:1 under the conditions of 37°C in a humidified atmosphere of 5% CO2 for seven days. Cell culture supernatants were collected at predetermined time points, and cell morphology was observed and photographed by microscopy. IL-1β was detected by ELISA. H838 and H1975 cells were treated with PBS or IL-1β for 24 hours. Cells were harvested and lysed, then analyzed in a proteome profiler array.

RESULTS:

Cells in co-cultures initially grew well. IL-1β was almost undetectable in lung cancer cell lines and macrophage monoculture groups but was highly expressed in co-cultures after 24h and declined at the 7th day. In the H838 and H1975 co-culture group, the lung cancer cells occupied a great majority. IL-1β activates the NF-κB pathway on H838 and H1975 cells.

CONCLUSION:

Our data showed that in a lung cancer co-culture incorporating lung cancer cells and macrophages lead to a higher expression of IL-1β than monoculture. It is possible that such dynamic changes in IL-1β expression may also occur in vivo in response to changes in the tumor microenvironment and interactions with immune cell populations. These interactions are likely important components to be considered when studying and modeling the expression of IL-1β as a potential therapeutic target in lung cancer.

• Authors: Dong Liu, Xiao-Qing Liu, Rosemarie Kiefl, Wei Zhang, Yin-Hui Xu, Amanda Tufman
• Journal: Annals of clinical and laboratory science (Ann Clin Lab Sci) Vol. 51 Issue 3 Pg. 295-301 (May 2021) ISSN: 1550-8080 [Electronic] United States
• PMID: 34162558 (Publication Type: Journal Article)
• Copyright: © 2021 by the Association of Clinical Scientists, Inc.

Chemical References

• IL1B protein, human
• Interleukin-1beta
• NF-kappa B

Topics

• Apoptosis
• Carcinoma, Non-Small-Cell Lung (drug therapy, immunology, metabolism, pathology)
• Cell Proliferation
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Interleukin-1beta (pharmacology)
• Lung Neoplasms (drug therapy, immunology, metabolism, pathology)
• Macrophages (immunology)
• NF-kappa B (agonists)
• Tumor Cells, Cultured
• Tumor Microenvironment