Lung cancer continues to be the leading cause of cancer-related deaths worldwide due to its high incidence, malignant behaviour and lack of major advancements in treatment strategy. The occurrence and development of lung cancer is closely related to inflammation. Thus, we conducted the present study to investigate the effects of IL-38 (interleukin-38), a newly identified anti-inflammatory factor, on non-small cell lung cancer (NSCLC), which accounts for about 85% of all lung cancers. We first evaluated the IL-38 expression in 384 pairs of NSCLC samples and their adjacent normal mucosa by real-time PCR, ELISA (enzyme-linked immunoassay) and tissue microarrays. Then the role of IL-38 on patient survival rates, cancer progression and their sensitivity to chemotherapy drugs was assessed. IL-38 was barely expressed in the NSCLC tissues but highly expressed in the adjacent normal tissues. The downregulation of IL-38 was significantly correlated with the results of the American Joint Committee on Cancer stage and degree of differentiation, and it was also shown to be an independent prognostic indicator of disease-free survival and overall survival for patients with NSCLC. Overexpression of IL-38 in NSCLC cells suppressed cell migration, invasion, proliferation and colony formation through suppressing β-catenin. IL-38 inhibited NSCLC formation in a mice model and sensitized the cancer cells to chemotherapy drugs. Our results show that IL-38 plays an inhibitory role in NSCLC development and functions as a novel prognostic indicator and a potential therapeutic target.

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