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

IF 2.8 4区医学 Q2 PHARMACOLOGY & PHARMACY Journal of Pharmacy and Pharmacology Pub Date : 2024-10-11 DOI:10.1093/jpp/rgae115

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

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引用次数: 0

摘要

研究目的大黄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。但关于大黄治疗胃癌（GC）的机制报道有限。本研究采用网络药理学结合体外实验的方法系统研究了大黄的作用机制：网络药理学证实了 Rhein 治疗 GC 的主要作用信号通路和关键靶点。细胞活力检测、集落形成检测、荧光探针检测、细胞凋亡检测、Western blot和qRT-PCR验证了Rhein治疗GC细胞（AGS和MGC803细胞）的机制：结果表明，大黄霉素通过调节Ras/磷酸肌醇-3激酶（PI3K）/蛋白激酶B（AKT）和p38/介原激活蛋白激酶信号通路，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）抑制了Rhein诱导的细胞凋亡：所有结果都证明，Rhein 可被视为治疗 GC 的潜在天然药物。

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

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.

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来源期刊

Journal of Pharmacy and Pharmacology 医学-药学

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： JPP keeps pace with new research on how drug action may be optimized by new technologies, and attention is given to understanding and improving drug interactions in the body. At the same time, the journal maintains its established and well-respected core strengths in areas such as pharmaceutics and drug delivery, experimental and clinical pharmacology, biopharmaceutics and drug disposition, and drugs from natural sources. JPP publishes at least one special issue on a topical theme each year.