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Liu, Dong; Liu, Xiao-qing; Kiefl, Rosemarie; Zhang, Wei; Xu, Yin-hui and Tufman, Amanda (2021): Effects of the NF-kappa B Pathway Agonist IL-1 beta on Non-Small Cell Lung Cancer Cell Lines. In: Annals of Clinical and Laboratory Science, Vol. 51, No. 3: pp. 295-301

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Objective. Canakinumab is an interleukin (IL)-1 beta 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-1 beta and the effect of IL-1 beta on the NF-kappa B 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 degrees 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-1 beta was detected by ELISA. H838 and H1975 cells were treated with PBS or IL-1 beta for 24 hours. Cells were harvested and lysed, then analyzed in a proteome profiler array. Results. Cells in co-cultures initially grew well. IL-1 beta 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-1 beta activates the NF-kappa B 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-1 beta than monoculture. It is possible that such dynamic changes in IL-1 beta 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-1 beta as a potential therapeutic target in lung cancer.

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