J Appl Biomed 16:15-21, 2018 | DOI: 10.1016/j.jab.2017.04.001

IL-37 mediates the anti-tumor activity in non-small cell lung cancer through IL-6/STAT3 pathway

Yan-Ming Deng, Hua Zhang, Jian-Miao Liang, Hai-Bing Xian, Ze-Cheng Chen, Yi-Cong Tang, Shuang Yang, Wei-Neng Feng^*

First People's Hospital of Foshan, Department of Head, Neck and Chest Oncology, PR China

The occurrence and development of lung cancer is closely related to inflammation. Thus, we conducted the present study to investigate the effects of IL-37 (Interleukin 37), a newly identified anti-inflammatory factor, on non-small cell lung cancer (NSCLC), which accounts for about 85% of all lung cancers. To address the function of IL-37 in NSCLC, we first evaluated IL-37 expression in the human NSCLC tissues; then the IL-37 function was assessed in vitro and in vivo in a xenografted lung tumor model. IL-37 was barely expressed in the NSCLC tissue but highly expressed in the adjacent normal tissue. This expression profile was validated by ELISA (Enzyme-linked immunoassay), western blot and immunohistochemical staining. Recombinant IL-37 could suppress cell migration, invasion and proliferation and promote cell apoptosis in NSCLC cell line A549 and SK-MES-1. IL-37 inhibited the IL-6/STAT3 pathway and also the downstream targets Bcl-2, NEDD9 and Cyclin D1. Overexpressing IL-6 or constitutive active STAT3 eliminated the anti-tumor effects of IL-37. Furthermore, IL-37 expression in vivo could inhibit the cancer development. Our results showed that IL-37 plays an inhibitory role in lung cancer development, possibly through IL-6/STAT3 pathway.

Keywords: Interleukin-37; Non-small cell lung cancer; IL-6, STAT3 pathway; IL-37; NSCLC

Received: December 23, 2016; Accepted: April 13, 2017; Published: February 1, 2018  Show citation