一种基于网络药理学的方法来研究脱氢木香内酯通过调节PI3K/Akt和细胞外信号调节激酶/丝裂原活化蛋白激酶信号通路抑制人胃癌细胞的增殖和上皮-间质转化。

A network pharmacology approach to investigate dehydrocostus lactone inhibits the proliferation and epithelial-mesenchymal transition of human gastric cancer cells via regulating the PI3K/Akt and extracellular signal-regulated kinases/mitogen-activated protein kinase signalling pathways.

作者信息

Wan Meiqi, Dai Jun, Gan Anna, Wang Jinyu, Lin Fei, Zhang Xiaoying, Lv Xinyan, Wu Bo, Yan Tingxu, Jia Ying

机构信息

Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, China.

School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, China.

出版信息

J Pharm Pharmacol. 2023 Oct 5;75(10):1344-1356. doi: 10.1093/jpp/rgad065.

DOI:10.1093/jpp/rgad065

PMID:37403268

Abstract

OBJECTIVES

Dehydrocostus lactone (DHE), a sesquiterpene lactone, has been proven the significant inhibition of multiple cancer cells. However, there are limited reports on the activity of DHE in gastric cancer (GC). In this research, Network pharmacology predicted the anti-GC mechanism of DHE, and the prediction was verified by in-vitro experiments.

METHODS

Network pharmacology confirmed the major effect signalling pathway of DHE in treating GC. Cell viability assay, colony formation assay, wound healing assay, cell migration and invasion assay, apoptosis assay, western blot and real-time quantitative polymerase chain reaction verified the mechanism of DHE in GC cell lines.

KEY FINDINGS

The results showed that DHE inhibited the growth and metastasis of MGC803 and AGS GC cells. Mechanistically, the analysis results indicated that DHE significantly induced the apoptosis process by suppressing the PI3K/protein kinase B (Akt) signalling pathway, and inhibited epithelial-mesenchymal transition by suppressing the extracellular signal-regulated kinases (ERK)/MAPK signalling pathway. The Akt activator (SC79) inhibited DHE induced apoptosis, and DHE had similar effects with the ERK inhibitor (FR180204).

CONCLUSIONS

All results suggested that DHE was a potential natural chemotherapeutic drug in GC treatment.

摘要

目的

脱氢木香内酯（DHE）是一种倍半萜内酯，已被证明对多种癌细胞具有显著抑制作用。然而，关于DHE在胃癌（GC）中的活性报道有限。在本研究中，网络药理学预测了DHE的抗GC机制，并通过体外实验对该预测进行了验证。

方法

网络药理学确定了DHE治疗GC的主要效应信号通路。细胞活力测定、集落形成测定、伤口愈合测定、细胞迁移和侵袭测定、凋亡测定、蛋白质免疫印迹法和实时定量聚合酶链反应验证了DHE在GC细胞系中的作用机制。

主要发现

结果表明，DHE抑制MGC803和AGS GC细胞的生长和转移。机制上，分析结果表明，DHE通过抑制PI3K/蛋白激酶B（Akt）信号通路显著诱导凋亡过程，并通过抑制细胞外信号调节激酶（ERK）/丝裂原活化蛋白激酶（MAPK）信号通路抑制上皮-间质转化。Akt激活剂（SC79）抑制DHE诱导的凋亡，且DHE与ERK抑制剂（FR180204）具有相似作用。