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.

据报道，五环三萜蒲公英醇（TAX）具有强大的抗肿瘤活性。但是，TAX在胃癌（GC）中的作用和分子机制仍未得到证实。应用网络药理学方法确定TAX和GC的共同目标。裸鼠皮下注射MKN-28细胞，建立GC皮下异种移植模型，用TAX处理16天。然后每隔一天检查一次肿瘤体积。用苏木精和曙红（H＆E）染色评估病理评分，并通过免疫组织化学分析确定Ki-67的表达水平和TAX的靶基因。确定了TAX和GC的五个共同目标，例如表皮生长因子受体（EGFR），基质金属蛋白酶2（MMP2），B-Raf原癌基因，丝氨酸/苏氨酸激酶（BRAF），成纤维细胞生长因子受体2（FGFR2）和AKT丝氨酸/苏氨酸激酶1（AKT1）。进一步的研究表明，与未治疗组相比，施用TAX抑制异种移植肿瘤的生长并降低Ki-67水平，然后下调异种移植肿瘤组织中EGFR和AKT1的表达。我们的发现表明，TAX通过抑制EGFR / AKT1信号传导来抑制GC的生长，并可能为GC的治疗提供新的治疗策略。与未治疗组相比，异种移植肿瘤组织中的EGFR和AKT1表达下调。我们的发现表明，TAX通过抑制EGFR / AKT1信号传导来抑制GC的生长，并可能为GC的治疗提供新的治疗策略。与未治疗组相比，异种移植肿瘤组织中的EGFR和AKT1表达下调。我们的发现表明，TAX通过抑制EGFR / AKT1信号传导来抑制GC的生长，并可能为GC的治疗提供新的治疗策略。