Solamargine inhibits gastric cancer progression via inactivation of STAT3/PD‑L1 signaling.

Abstract

Gastric cancer (GC) is characterized by a high mortality rate (70%) worldwide. Programmed cell death‑1 and its ligand, programmed cell death ligand 1 (PD‑L1), are vital immune checkpoints, which serve a notable role in GC. Solamargine, an extract from traditional Chinese medicine Long Kui, exerts suppressive effects on several types of cancer including cervical, lung and prostate cancer. However, the association between solamargine and PD‑L1 in GC remains unclear. Therefore, the present study aimed to investigate the underlying mechanism of solamargine on GC. Specifically, 5‑ethynyl‑2'‑deoxyuridine and Transwell assays were performed to assess GC cell proliferation, invasion and migration. Additionally, GC cells (HGC‑827 and NCI‑N87) were stimulated with 20 ng/ml recombinant human IL‑6 for 24 h, before the protein expression levels of PD‑L1 were measured using western blot analysis. Furthermore, T cell function was evaluated through incubation of Jurkat T cells with solamargine. The results demonstrated that solamargine could markedly inhibit GC cell proliferation, migration and invasion, by inhibiting STAT3 signaling. In addition, GC cell treatment with solamargine downregulated the expression of PD‑L1. Furthermore, solamargine reversed the IL‑6‑induced PD‑L1 upregulation in GC cells by downregulating STAT3 activity. Additionally, the results demonstrated that solamargine inhibited IL‑6‑induced PD‑L1 upregulation of GC cells. This suggests that solamargine exerted an immunostimulatory activity in GC. In conclusion, the present study indicated that solamargine may inhibit the progression of GC by suppressing STAT3/PD‑L1 signaling. Therefore, treatment with solamargine may serve as novel strategy for the treatment of GC.