IL‑33/ST2 promotes the malignant progression of gastric cancer via the MAPK pathway.

Abstract

Gastric cancer (GC) remains one of the commonest malignant tumors and the second leading cause of cancer-related deaths worldwide. IL-33 is highly expressed in tumor tissues and serum of patients with GC. However, the function of the IL-33 and IL-33 receptor ST2 in the malignant progression of GC is yet to be elucidated. The present study aimed to explore the effect of the IL-33/ST2 axis on the biological functions of GC cells. The expression of ST2 in GC tissues was measured by immunohistochemistry. GC cell lines (AGS and MKN45) were treated with IL-33, and the expression of ST2 was downregulated by using specific siRNA. The effects of the IL-33/ST2 axis on cell proliferation, migration, invasion, cell cycle and apoptosis was detected by CCK8, Transwell, wound healing, flow cytometry and western blotting assays. The present study found that ST2 was highly expressed in GC tissues compared with normal tissues. IL-33 promoted the proliferation and cell cycle progression of GC cells, and upregulated the expression levels of CDK4, CDK6 and cyclin D1. Furthermore, IL-33 inhibited the apoptosis of GC cells and regulated the expression of apoptosis-associated proteins. In addition, IL-33 stimulated the invasion and migration of GC cells. However, the transfection of ST2 small interfering (si)RNA attenuated the effects of IL-33. Finally, IL-33 stimulation increased the phosphorylation levels of ERK1/2, JNK and p38. The transfection of ST2 siRNA could significantly inhibit the IL-33-induced ERK1/2, JNK and p38 activation. In conclusion, it was found that ST2 was highly expressed in GC tissues. IL-33/ST2 promoted the malignant progression of GC cells by inducing the activation of ERK1/2, JNK and p38.