Network pharmacology-based identification of the antitumor effects of taraxasterol in gastric cancer

Abstract

Taraxasterol (TAX), a pentacyclic triterpene, has been reported to exhibit potent antitumor activity. However, the effects and molecular mechanisms of TAX in gastric cancer (GC) remain undocumented. A network pharmacology approach was applied to identify the collective targets of TAX and GC. Nude mice were subcutaneously injected with MKN-28 cells to establish GC subcutaneous xenograft model, which were treated with TAX for 16 days. Tumor volume was then examined every other day. The pathological scoring was assessed by using hematoxylin and eosin (H&E) staining, and the expression levels of Ki-67 and the target genes of TAX were confirmed by immunohistochemistry analysis. Five collective targets of TAX and GC were identified, such as epidermal growth factor receptor (EGFR), matrix metalloproteinase 2 (MMP2), B-Raf proto-oncogene, serine/threonine kinase (BRAF), fibroblast growth factor receptor 2 (FGFR2), and AKT serine/threonine kinase 1 (AKT1). Further investigations showed that, TAX administration repressed xenograft tumor growth and decreased Ki-67 levels, followed by the downregulation of EGFR and AKT1 expression in xenograft tumor tissues as compared with the untreated group. Our findings demonstrated that TAX inhibited the growth of GC by inhibition of EGFR/AKT1 signaling and might provide a novel therapeutic strategy for treatment of GC.