In:
Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-2-14)
Abstract:
This study aimed to identify the mechanism of Yiqi Huayu Decoction (YQHY) induced ferroptosis in gastric cancer (GC) by using network pharmacology and experimental validation. Methods The targets of YQHY, ferroptosis-related targets, and targets related to GC were derived from databases. Following the protein–protein interaction (PPI) network, the hub targets for YQHY induced ferroptosis in GC were identified. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to analyze the hub targets from a macro perspective. We verified the hub targets by molecular docking, GEPIA, HPA, and the cBioPortal database. Finally, we performed cell viability assays, quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, lipid peroxidation, and GSH assays to explore the mechanism of YQHY induced ferroptosis in GC. Results We identified the main active compounds and hub targets: Quercetin, DIBP, DBP, Mipax, Phaseol and TP53, ATM, SMAD4, PTGS2, and ACSL4. KEGG enrichment analyses indicated that the JAK2-STAT3 signaling pathway may be a significant pathway. Molecular docking results showed that the main active compounds had a good binding activity with the hub targets. The experimental results proved that YQHY could induce ferroptosis in AGS by increasing the MDA content and reducing the GSH content. qRT–PCR and Western blot results showed that YQHY can induce ferroptosis in GC by affecting the JAK2-STAT3 pathway and the expression of ACSL4. Conclusions This study indicated that YQHY can induce ferroptosis in GC by affecting the JAK2–STAT3 pathway and the expression of ACSL4, and induction of ferroptosis may be one of the possible mechanisms of YQHY’s anti-recurrence and metastasis of GC.
Type of Medium:
Online Resource
ISSN:
2234-943X
DOI:
10.3389/fonc.2022.820059
DOI:
10.3389/fonc.2022.820059.s001
DOI:
10.3389/fonc.2022.820059.s002
DOI:
10.3389/fonc.2022.820059.s003
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10.3389/fonc.2022.820059.s004
DOI:
10.3389/fonc.2022.820059.s005
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10.3389/fonc.2022.820059.s006
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10.3389/fonc.2022.820059.s007
DOI:
10.3389/fonc.2022.820059.s008
DOI:
10.3389/fonc.2022.820059.s009
DOI:
10.3389/fonc.2022.820059.s010
DOI:
10.3389/fonc.2022.820059.s011
DOI:
10.3389/fonc.2022.820059.s012
DOI:
10.3389/fonc.2022.820059.s013
DOI:
10.3389/fonc.2022.820059.s014
DOI:
10.3389/fonc.2022.820059.s015
DOI:
10.3389/fonc.2022.820059.s016
DOI:
10.3389/fonc.2022.820059.s017
DOI:
10.3389/fonc.2022.820059.s018
DOI:
10.3389/fonc.2022.820059.s019
DOI:
10.3389/fonc.2022.820059.s020
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2649216-7
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