Dioscin Impedes Proliferation, Metastasis and Enhances Autophagy of Gastric Cancer Cells via Regulating the USP8/TGM2 Pathway.

Gastric cancer (GC) is one of the most common cancers worldwide. Dioscin has been shown to have anti-cancer effects in GC. The aim of this study is to explore a novel mechanism of dioscin in repressing GC progression. Cell viability, proliferation, apoptosis and invasion were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry and transwell assays, respectively. Monodansylcadaverine (MDC) staining was used to assess cell autophagy. The expression of transglutaminase-2 (TGM2), ubiquitin-specific peptidase 8 (USP8) and autophagy-related proteins was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. A xenograft tumor model was established to investigate the function of dioscin in vivo. Dioscin inhibited GC cell proliferation and invasion, but induced apoptosis and autophagy. TGM2 was highly expressed in GC, and dioscin suppressed GC progression by decreasing the protein level of TGM2. Furthermore, USP8 positively regulated TGM2 expression, and TGM2 overexpression reversed the inhibitory effect of USP8 knockdown on GC cell progression. USP8 abated the effect of dioscin in GC cells. Dioscin decreased the protein level of TGM2 via regulating USP8. In addition, dioscin restrained GC tumor growth in vivo. Dioscin played an anti-cancer effect in GC by enhancing cancer cell autophagy via regulating the USP8/TGM2 pathway.