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大黄酸通过调节Ras/PI3K/AKT和p38/MAPK信号通路诱导AGS和MGC803细胞凋亡。

Rhein induces apoptosis of AGS and MGC803 cells by regulating the Ras/PI3K/AKT and p38/MAPK signaling pathway.

作者信息

Wan Meiqi, Gan Anna, Dai Jun, Lin Fei, Wang Ruixuan, Wu Bo, Yan Tingxu, Jia Ying

机构信息

Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, China.

出版信息

J Pharm Pharmacol. 2025 Jun 9;77(6):783-793. doi: 10.1093/jpp/rgae115.

Abstract

OBJECTIVES

Rhein is one of the main bioactive compounds in the Polygonaceae plant, and has been proven to have anti-cancer activity in some reports. But the mechanism of Rhein in the treatment of gastric cancer (GC) is limited reported. In this research, network pharmacology combined with in vitro experiments was used for systematically studying the mechanism of Rhein.

METHODS

Network pharmacology confirmed the major effect signaling pathway and key targets of Rhein in the treatment of GC. Cell viability assay, colony formation assay, fluorescence probe assay, apoptosis assay, western blot and qRT-PCR verified the mechanism of Rhein in the treatment of GC cells (AGS and MGC803 cells).

KEY FINDINGS

The results showed that Rhein significantly induced the apoptosis process of AGS and MGC803 cells by regulating the Ras/phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT) and the p38/mitogen-activated protein kinase signaling pathways. The AKT activator (SC79) and p38 inhibitor (SB202190) inhibited Rhein-induced apoptosis.

CONCLUSIONS

All results proved that Rhein could be recognized as a potential natural drug for the treatment of GC.

摘要

目的

大黄素是蓼科植物中的主要生物活性化合物之一,一些报道已证实其具有抗癌活性。但大黄素治疗胃癌(GC)的机制报道有限。本研究采用网络药理学结合体外实验系统地研究大黄素的作用机制。

方法

网络药理学确定大黄素治疗GC的主要效应信号通路和关键靶点。细胞活力测定、集落形成测定、荧光探针测定、凋亡测定、蛋白质印迹法和定量逆转录聚合酶链反应验证大黄素治疗GC细胞(AGS和MGC803细胞)的机制。

主要发现

结果表明,大黄素通过调节Ras/磷酸肌醇-3激酶(PI3K)/蛋白激酶B(AKT)和p38/丝裂原活化蛋白激酶信号通路,显著诱导AGS和MGC803细胞的凋亡过程。AKT激活剂(SC79)和p38抑制剂(SB202190)抑制大黄素诱导的凋亡。

结论

所有结果证明大黄素可被视为一种治疗GC的潜在天然药物。

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