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      Systematic Elucidation of the Mechanism of Quercetin against Gastric Cancer via Network Pharmacology Approach

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          This study was aimed at elucidating the potential mechanisms of quercetin in the treatment of gastric cancer (GC). A network pharmacology approach was used to analyze the targets and pathways of quercetin in treating GC. The predicted targets of quercetin against GC were obtained through database mining, and the correlation of these targets with GC was analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Next, the protein-protein interaction (PPI) network was constructed, and overall survival (OS) analysis of hub targets was performed using the Kaplan–Meier Plotter online tool. Finally, the mechanism was further analyzed via molecular docking of quercetin with the hub targets. Thirty-six quercetin-related genes were identified, 15 of which overlapped with GC-related targets. These targets were further mapped to 319 GO biological process terms and 10 remarkable pathways. In the PPI network analysis, six hub targets were identified, including AKT1, EGFR, SRC, IGF1R, PTK2, and KDR. The high expression of these targets was related to poor OS in GC patients. Molecular docking analysis confirmed that quercetin can bind to these hub targets. In conclusion, this study provided a novel approach to reveal the therapeutic mechanisms of quercetin on GC, which will ease the future clinical application of quercetin in the treatment of GC.

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            Reactive species, which mainly include reactive oxygen species (ROS), are products generated as a consequence of metabolic reactions in the mitochondria of eukaryotic cells. In normal cells, low-level concentrations of these compounds are required for signal transduction before their elimination. However, cancer cells, which exhibit an accelerated metabolism, demand high ROS concentrations to maintain their high proliferation rate. Different ways of developing ROS resistance include the execution of alternative pathways, which can avoid large amounts of ROS accumulation without compromising the energy demand required by cancer cells. Examples of these processes include the guidance of the glycolytic pathway into the pentose phosphate pathway (PPP) and/or the generation of lactate instead of employing aerobic respiration in the mitochondria. Importantly, ROS levels can be used as a thermostat to monitor the damage that cells can bear. The implications for ROS regulation are highly significant for cancer therapy because commonly used radio- and chemotherapeutic drugs influence tumor outcome through ROS modulation. Moreover, the discovery of novel biomarkers that are able to predict the clinical response to pro-oxidant therapies is a crucial challenge to overcome to allow for the personalization of cancer therapies. Copyright © 2012 Elsevier B.V. All rights reserved.
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                Author and article information

                Biomed Res Int
                Biomed Res Int
                BioMed Research International
                3 September 2020
                : 2020
                1Department of Gastroenterology, Tongde Hospital of Zhejiang Province, Hangzhou 310012, China
                2Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
                3Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
                4Guangdong Province Engineering Technology Research Institute of T.C.M., Guangzhou 510095, China
                Author notes

                Academic Editor: Susan A. Rotenberg

                Copyright © 2020 Liangjun Yang et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Funded by: 13th Five-Year Plan of Zhejiang Provincial Key Discipline Construction of Traditional Chinese Medicine
                Award ID: 2017-XK-B02
                Funded by: Characteristic Innovation Projects of Ordinary Universities in Guangdong Province
                Award ID: 2018KTSCX040
                Funded by: National Natural Science Foundation of China
                Award ID: 81973816
                Award ID: 81673946
                Research Article


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