Li Jiawei, Li Fangfang, Zhao Yuqing, Jin Dan
Immunology Biology Key Laboratory, Yanbian University, Yanji, China.
Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, China.
Front Pharmacol. 2023 May 22;14:1159712. doi: 10.3389/fphar.2023.1159712. eCollection 2023.
20 (R)-25-methoxyl-dammarane-3β, 12β, 20-triol (AD-1), a novel ginsenoside isolated from stem and leaf of Panax Notoginseng, has anticancer activity against a variety of malignant tumors. However, the pharmacological mechanism of AD-1 on colorectal cancer (CRC) remains unclear. The purpose of this study was to verify the potential mechanism of action of AD-1 against CRC through network pharmacology and experiments. A total of 39 potential targets were obtained based on the intersection of AD-1 and CRC targets, and key genes were analyzed and identified from the PPI network using Cytoscape software. 39 targets were significantly enriched in 156 GO terms and 138 KEGG pathways, among which PI3K-Akt signaling pathway was identified as one of the most enriched pathways. Based on experimental results, AD-1 can inhibit the proliferation and migration of SW620 and HT-29 cells, and induce their apoptosis. Subsequently, the HPA and UALCAN databases showed that PI3K and Akt were highly expressed in CRC. AD-1 also decreased the expressions of PI3K and Akt. In summary, these results suggest that AD-1 can play an anti-tumor role by inducing cell apoptosis and regulating PI3K-Akt signaling pathway.
20（R）-25-甲氧基-达玛烷-3β，12β，20-三醇（AD-1）是从三七茎叶中分离得到的一种新型人参皂苷，对多种恶性肿瘤具有抗癌活性。然而，AD-1对结直肠癌（CRC）的药理机制尚不清楚。本研究旨在通过网络药理学和实验验证AD-1对CRC的潜在作用机制。基于AD-1与CRC靶点的交集共获得39个潜在靶点，并使用Cytoscape软件从蛋白质-蛋白质相互作用（PPI）网络中分析和鉴定关键基因。39个靶点在156个基因本体（GO）术语和138条京都基因与基因组百科全书（KEGG）通路中显著富集，其中PI3K-Akt信号通路被确定为最富集的通路之一。基于实验结果，AD-1可抑制SW620和HT-29细胞的增殖和迁移，并诱导其凋亡。随后，人类蛋白质图谱（HPA）和UALCAN数据库显示PI3K和Akt在CRC中高表达。AD-1也降低了PI3K和Akt的表达。综上所述，这些结果表明AD-1可通过诱导细胞凋亡和调节PI3K-Akt信号通路发挥抗肿瘤作用。
