Hydroxysafflor Yellow A of Carthamus Tinctorius L., Represses the Malignant Development of Esophageal Cancer Cells via Regulating NF-κB Signaling Pathway

Esophageal cancer (EC) is a common digestive tract malignant tumor and the clinical outcome of patients with EC after surgery remains unsatisfactory. Hence, it is necessary to identify some effective drugs or methods to improve the prognosis of patients with EC. In this study, we attempted to analyze the potential role of hydroxysafflor yellow A (HSYA) in EC. Combined with The Cancer Genome Atlas (TCGA) and Comparative Toxicogenomics Database (CTD) as well as Database for Annotation, Visualization, and Integrated Discovery (DAVID) website, we tried to identify the related genes and pathways of HSYA. Then we estimated the actions of HSYA on proliferation, invasion and migration, and apoptosis of EC cells using cell counting kit 8, transwell and flow cytometry assays, respectively. At last, the expression of inflammatory protein and signaling pathway-related protein were measured using western blot analysis. Relative protein expression of intercellular adhesion molecule 1 (ICAM1), matrix metallopeptidase 9 (MMP9), tumor necrosis factor (TNF), and vascular cell adhesion molecule 1 (VCAM1) were all upregulated in EC tissues compared with normal tissues and they might be the target gene of HSYA according to bioinformatics analysis. HSYA exerted an inhibitory actions on cells proliferation, invasion, and migration but could accelerate the apoptosis of cells in EC. Moreover, HSYA could inhibit the expression of ICAM1, MMP9, TNF-α, and VCAM1 and induced the expression of phosphor-nuclear transcription factor kappa B p65 (p-P65) and phosphor-I kappa B-alpha (p-IκBα), but it did not influence the expression of P65 and IκBα. HSYA suppressed proliferation, invasion, and migration, simultaneously induce apoptosis of EC cells partly via regulating NF-κB signaling pathway.

Keywords: Apoptosis; Cell invasion; Cell migration; Cellular proliferation; Esophageal cancer; Hydroxysafflor yellow A (HSYA).