Abstract
Gastric cancer (GC) is a prevalent malignancy of gastrointestinal tract with a high incidence worldwide. Polydatin, a bioactive compound in Polygonum cuspidatum, possesses antitumor effects. We aimed to study the role of polydatin in GC and its possible mechanism. HGC27 cells were treated with varying doses of polydatin, and cell viability was tested by CCK-8 assay. Colony formation assay and immunofluorescence staining of Ki67 were employed to evaluate the proliferation of HGC27 cells. Sphere formation assay was conducted to analyze the stemness of HGC27 cells and levels of genes related to stemness was tested by RT-qPCR and immunoblotting. Additionally, angiogenesis was assessed by performing tube formation assay and examining VEGF secretion. Then, histone deacetylase 7 (HDAC7) was upregulated in polydatin-treated HGC27 cells to explore the regulatory effect of polydatin on HDAC7. Results suggested that polydatin gradually reduced the viability and suppressed the proliferation of HGC27 cells with the increase of polydatin concentrations. Notably, polydatin dose-dependently decreased sphere formation in size, accompanied by downregulated SOX2 and OCT4 levels. Besides, the conditioned medium from polydatin treated HGC27 cells resulted in decreased VEGF secretion levels and tube formation capacities. Importantly, Super-PRED database and molecular docking predicted that HDAC7 was a downstream target that could combine with polydatin. Bioinformatics analysis indicated that HDAC7 expression was elevated in GC tissues and high HDAC7 expression predicted low prognosis. Moreover, polydatin downregulated HDAC7 expression in HGC27 cells. Particularly, HDAC7 upregulation blocked the influences of polydatin on proliferation, stemness and angiogenesis of HGC27 cells. Collectively, polydatin inhibits the stemness and angiogenesis of GC cells by targeting down-regulation of HDAC7.