Oxymatrine exhibits anti-tumor activity in gastric cancer through inhibition of IL-21R-mediated JAK2/STAT3 pathway.

Abstract

Oxymatrine (OMT) as a type of alkaloids collected from Sophora flavescens Ait exerts some biological functions including anticancer properties. Here, we investigated the therapeutic effects of OMT in gastric cancer cells (HGC 27 and AGS). As a result, the exposure of gastric cancer (GC) cells to OMT contributed to the suppression of cell proliferation and invasion. Interleukin 21 receptor (IL-21R) was identified to be differentially expressed between OMT treatment group (4 mg/mL) and control group (0 mg/mL), and knockdown of IL-21R repressed cell proliferation and invasion via inactivation of the JAK2/STAT3 pathway. The rescue experiment showed that IL-21R overexpression attenuated the anti-tumor effects of OMT through activation of the JAK2/STAT3 pathway. Moreover, the expression of IL-21R was significantly upregulated in GC samples compared with the adjacent normal tissues and associated with overall survival (OS) and tumor recurrence of GC patients. Taken together, in this study, we evaluated the anti-tumor effects of OMT on GC by investigating proliferation and invasion ability changes, and our findings show that OMT exhibits effects via regulation of JAK/STAT signaling pathway. Through the mechanism study, we may enlighten the potential therapeutic target for treatment of GC.