Abstract
Aim:
IL-37b has shown anti-cancer activities in addition to its anti-inflammatory properties. In this study, we investigated the effects of IL-37b on breast carcinoma growth in mice and to determine the involvement of T cell activation in the effects.
Methods:
IL-37b gene was transferred into mouse breast carcinoma cell line 4T1 (4T1-IL37b cells), the expression of secretory IL-37b by the cells was detected, and the effects of IL-37b expression on the cell proliferation in vitro was evaluated. After injection of 4T1 cells or 4T1-IL37b cells into immunocompetent BALB/c mice, immunodeficient BALB/c nude mice and NOD-SCID mice, the tumor growth and survival rate were measured. The proliferation of T cells in vitro was also detected.
Results:
IL-37b was detected in the supernatants of 4T1-IL37b cells with a concentration of 12.02±0.875 ng/mL. IL-37b expression did not affect 4T1 cell proliferation in vitro. BALB/c mice inoculated with 4T1-IL37b cells showed significant retardation of tumor growth. BALB/c mice inoculated with both 4T1 cells and mitomycin C-treated 4T1-IL37b cells also showed significant retardation of tumor growth. But the anti-cancer activity of IL-37b was abrogated in BALB/c nude mice and NOD-SCID mice inoculated with 4T1-IL37b cells. Recombinant IL-37b slightly promoted CD4+ T cell proliferation without affecting CD8+ T cell proliferation.
Conclusion:
IL-37b exerts anti-4T1 breast carcinoma effects in vivo by modulating the tumor microenvironment and influencing T cell activation.
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Acknowledgements
This work was supported by the National Basic Research Program of China (2013CB966904, 2015CB964402), the National Natural Science Foundation of China (81421002, 81273217, 81322007, 81170007), the Tianjin Research Program of Application Foundation and Advanced Technology (12JCYBJC32800), the Technology Foundation for Selected Overseas Chinese Scholars, the Fok Ying-Tong Education Foundation of China (131039), and the Recruitment Program of Global Youth Experts.
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Wang, Wq., Zhao, D., Zhou, Ys. et al. Transfer of the IL-37b gene elicits anti-tumor responses in mice bearing 4T1 breast cancer. Acta Pharmacol Sin 36, 528–534 (2015). https://doi.org/10.1038/aps.2015.3
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DOI: https://doi.org/10.1038/aps.2015.3
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