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Bioinformatics and network pharmacology identify promotional effects and potential mechanisms of ethanol on esophageal squamous cell carcinoma and experimental validation

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机构: [1]College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, China [2]The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
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关键词: Network Pharmacology Bioinformatics Ethanol Esophageal Squamous Cell Carcinoma 4-Nitroquinoline-1-Oxide

摘要:
Ethanol is an important risk factor for esophageal squamous cell carcinoma (ESCC); however, the molecular mechanisms behind how ethanol promotes ESCC development remain poorly understood. In this study, ethanol-ESCC-associated target genes were constructed and screened using network pharmacology and subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) and bioinformatics analysis. A mouse ethanol-exposed esophageal cancer model was constructed with 4-nitroquinoline-1-oxide (4-NQO) to assess its survival and tumor lesion status, and the mechanism of ethanol-promoted ESCC lesions was verified by qRT-PCR and Western blotting. The results showed that 126 ethanol-ESCC crossover genes were obtained, which were significantly enriched in the PI3K/AKT signaling pathway. Bioinformatics results showed that the target genes TNF, IL6, IL1β and JUN were highly expressed in esophageal tumor samples and positively correlated with tumor proliferation and apoptosis genes, and the genetic information of these genes was mutated to different degrees. Animal model experiments showed that ethanol decreased the survival rate and aggravated the occurrence of esophageal cancer in mice. qRT-PCR showed that ethanol promoted the expression of TNF, IL6, IL1β and JUN mRNA in mouse esophageal tumor tissues, and Western blotting showed that ethanol promoted p-PI3K and p-AKT protein expression in mouse esophageal tumor tissues. In conclusion, ethanol promotes esophageal carcinogenesis by increasing the expression of TNF, IL6, IL1β and JUN and activating the PI3K/AKT signaling pathway.Copyright © 2023. Published by Elsevier Inc.

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出版当年[2023]版:
大类 | 3 区 医学
小类 | 2 区 毒理学 3 区 药学
最新[2025]版:
大类 | 3 区 医学
小类 | 2 区 毒理学 3 区 药学
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出版当年[2023]版:
Q2 PHARMACOLOGY & PHARMACY Q2 TOXICOLOGY
最新[2023]版:
Q2 PHARMACOLOGY & PHARMACY Q2 TOXICOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2023版] 出版当年五年平均 出版前一年[2022版]

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第一作者机构: [1]College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, China
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通讯机构: [1]College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, China [2]The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China [*1]College of Integrated Chinese and Western Medicine, Hebei Medical University, 361 Zhongshan Road, Shijiazhuang, 050017, China. The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Chang'an District, Shijiazhuang, 050011, China.
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