Interleukin‐36α suppresses growth of non‐small cell lung cancer in vitro by reducing angiogenesis

Interleukin (IL)‐36α, a newly recognized IL‐1 family member, has been previously reported to play a pivotal role in autoimmunity diseases and acute inflammatory reactions. Recently, several studies have indicated that IL‐36α has potential anticancer effects against certain types of cancer. However, the expression pattern and functional role of IL‐36α in non‐small cell lung cancer (NSCLC) have not been elucidated. Here, we report that the mRNA and protein levels of IL‐36α are significantly reduced in NSCLC tissues. Low levels of intratumoral IL‐36α are correlated with higher tumor status, advanced TNM stage, increased vascular invasion and shorter overall survival (OS). Intratumoral IL‐36α expression is an independent prognostic factor for OS (hazard ratio = 3.081; P = 0.012) in patients with NSCLC. Overexpression of IL‐36α in lung cancer cells did not disturb cell proliferation, apoptosis or cell‐cycle distribution in vitro, but markedly inhibited tumor growth in vivo. Mechanistically, IL‐36α reduced the expression and secretion of vascular endothelial growth factor A through inhibiting hypoxia‐inducible factor 1α expression. Finally, decreased IL‐36α expression was associated with high microvessel density and vascular endothelial growth factor A in patients with NSCLC. Together, our findings suggest that IL‐36α expression is a valuable marker indicating poor prognosis in patients with NSCLC.