{"title":"化食解毒汤通过miRNA-21-3p/p53通路增强5-氟尿嘧啶治疗胃癌的疗效","authors":"Qianran Hong, Weiye Lin, Yici Yan, Shuangyu Chen, Jiayang Li, Jieru Yu, Ying Zhu, Shengliang Qiu","doi":"10.2147/DDDT.S513371","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>To explore the mechanism of Huashi Jiedu Decoction (HJD) synergizing with 5-fluorouracil (5-Fu) in gastric cancer (GC) therapy.</p><p><strong>Methods: </strong>MicroRNAs (miRNAs) and genes involved in HJD-mediated GC treatment were identified using ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap mass spectrometry, network pharmacology, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and molecular docking. The effects of HJD on 5-Fu sensitivity in BGC-823 cells were evaluated with 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, reverse transcription quantitative polymerase chain reaction (RT-qPCR), and Western blotting. Synergistic effects in vector-transfected and miRNA-21-3p knockdown cells were assessed by colony formation, wound healing, transwell assays, and flow cytometry (FCM). An in vivo study evaluated the impact of HJD on 5-Fu sensitivity, measuring miRNA-21-3p, tumor protein p53 (p53), N-cadherin, vimentin, and E-cadherin in tumors, along with tumor volume and weight.</p><p><strong>Results: </strong>miRNA-21-3p and p53 were key targets in HJD's therapeutic effect on GC. RT-qPCR showed that HJD combined with 5-Fu reduced miRNA-21-3p and upregulated p53 in vector cells and increased p53 mRNA (<i>p</i> < 0.01) and protein (<i>p</i> < 0.05) compared to 5-Fu alone. These effects were abolished in miRNA-21-3p knockdown cells. The combination reduced colony formation by 48.92% (<i>p</i> < 0.01), suppressed transwell migration by 28.5% (<i>p</i> < 0.01), and inhibited wound healing by 81.9% compared to 5-Fu monotherapy (<i>p</i> < 0.001), with no effects in knockdown cells. FCM showed a 15.1% increase in G<sub>0</sub>/G<sub>1</sub> phase arrest (<i>p</i> < 0.05). In vivo, the combination significantly reduced tumor volume (<i>p</i> < 0.05) and weight by 18.7%, with concomitant miRNA-21-3p downregulation (<i>p</i> < 0.0001), EMT marker suppression (N-cadherin, vimentin), and tumor suppressor activation (p53, E-cadherin) versus 5-Fu alone.</p><p><strong>Conclusion: </strong>HJD enhances 5-Fu's effects on GC by regulating the miRNA-21-3p/p53 pathway and modulating cadherin expression, supporting its potential as an adjunctive treatment in GC.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"3883-3906"},"PeriodicalIF":4.7000,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087606/pdf/","citationCount":"0","resultStr":"{\"title\":\"Huashi Jiedu Decoction Enhances 5-Fluorouracil Efficacy in Gastric Cancer via miRNA-21-3p/p53 Pathway.\",\"authors\":\"Qianran Hong, Weiye Lin, Yici Yan, Shuangyu Chen, Jiayang Li, Jieru Yu, Ying Zhu, Shengliang Qiu\",\"doi\":\"10.2147/DDDT.S513371\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>To explore the mechanism of Huashi Jiedu Decoction (HJD) synergizing with 5-fluorouracil (5-Fu) in gastric cancer (GC) therapy.</p><p><strong>Methods: </strong>MicroRNAs (miRNAs) and genes involved in HJD-mediated GC treatment were identified using ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap mass spectrometry, network pharmacology, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and molecular docking. The effects of HJD on 5-Fu sensitivity in BGC-823 cells were evaluated with 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, reverse transcription quantitative polymerase chain reaction (RT-qPCR), and Western blotting. Synergistic effects in vector-transfected and miRNA-21-3p knockdown cells were assessed by colony formation, wound healing, transwell assays, and flow cytometry (FCM). An in vivo study evaluated the impact of HJD on 5-Fu sensitivity, measuring miRNA-21-3p, tumor protein p53 (p53), N-cadherin, vimentin, and E-cadherin in tumors, along with tumor volume and weight.</p><p><strong>Results: </strong>miRNA-21-3p and p53 were key targets in HJD's therapeutic effect on GC. RT-qPCR showed that HJD combined with 5-Fu reduced miRNA-21-3p and upregulated p53 in vector cells and increased p53 mRNA (<i>p</i> < 0.01) and protein (<i>p</i> < 0.05) compared to 5-Fu alone. These effects were abolished in miRNA-21-3p knockdown cells. The combination reduced colony formation by 48.92% (<i>p</i> < 0.01), suppressed transwell migration by 28.5% (<i>p</i> < 0.01), and inhibited wound healing by 81.9% compared to 5-Fu monotherapy (<i>p</i> < 0.001), with no effects in knockdown cells. FCM showed a 15.1% increase in G<sub>0</sub>/G<sub>1</sub> phase arrest (<i>p</i> < 0.05). In vivo, the combination significantly reduced tumor volume (<i>p</i> < 0.05) and weight by 18.7%, with concomitant miRNA-21-3p downregulation (<i>p</i> < 0.0001), EMT marker suppression (N-cadherin, vimentin), and tumor suppressor activation (p53, E-cadherin) versus 5-Fu alone.</p><p><strong>Conclusion: </strong>HJD enhances 5-Fu's effects on GC by regulating the miRNA-21-3p/p53 pathway and modulating cadherin expression, supporting its potential as an adjunctive treatment in GC.</p>\",\"PeriodicalId\":11290,\"journal\":{\"name\":\"Drug Design, Development and Therapy\",\"volume\":\"19 \",\"pages\":\"3883-3906\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2025-05-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087606/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug Design, Development and Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/DDDT.S513371\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Design, Development and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/DDDT.S513371","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Huashi Jiedu Decoction Enhances 5-Fluorouracil Efficacy in Gastric Cancer via miRNA-21-3p/p53 Pathway.
Purpose: To explore the mechanism of Huashi Jiedu Decoction (HJD) synergizing with 5-fluorouracil (5-Fu) in gastric cancer (GC) therapy.
Methods: MicroRNAs (miRNAs) and genes involved in HJD-mediated GC treatment were identified using ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap mass spectrometry, network pharmacology, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and molecular docking. The effects of HJD on 5-Fu sensitivity in BGC-823 cells were evaluated with 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, reverse transcription quantitative polymerase chain reaction (RT-qPCR), and Western blotting. Synergistic effects in vector-transfected and miRNA-21-3p knockdown cells were assessed by colony formation, wound healing, transwell assays, and flow cytometry (FCM). An in vivo study evaluated the impact of HJD on 5-Fu sensitivity, measuring miRNA-21-3p, tumor protein p53 (p53), N-cadherin, vimentin, and E-cadherin in tumors, along with tumor volume and weight.
Results: miRNA-21-3p and p53 were key targets in HJD's therapeutic effect on GC. RT-qPCR showed that HJD combined with 5-Fu reduced miRNA-21-3p and upregulated p53 in vector cells and increased p53 mRNA (p < 0.01) and protein (p < 0.05) compared to 5-Fu alone. These effects were abolished in miRNA-21-3p knockdown cells. The combination reduced colony formation by 48.92% (p < 0.01), suppressed transwell migration by 28.5% (p < 0.01), and inhibited wound healing by 81.9% compared to 5-Fu monotherapy (p < 0.001), with no effects in knockdown cells. FCM showed a 15.1% increase in G0/G1 phase arrest (p < 0.05). In vivo, the combination significantly reduced tumor volume (p < 0.05) and weight by 18.7%, with concomitant miRNA-21-3p downregulation (p < 0.0001), EMT marker suppression (N-cadherin, vimentin), and tumor suppressor activation (p53, E-cadherin) versus 5-Fu alone.
Conclusion: HJD enhances 5-Fu's effects on GC by regulating the miRNA-21-3p/p53 pathway and modulating cadherin expression, supporting its potential as an adjunctive treatment in GC.
期刊介绍：
Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications.
The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas.
Specific topics covered by the journal include:
Drug target identification and validation
Phenotypic screening and target deconvolution
Biochemical analyses of drug targets and their pathways
New methods or relevant applications in molecular/drug design and computer-aided drug discovery*
Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes)
Structural or molecular biological studies elucidating molecular recognition processes
Fragment-based drug discovery
Pharmaceutical/red biotechnology
Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products**
Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development
Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing)
Preclinical development studies
Translational animal models
Mechanisms of action and signalling pathways
Toxicology
Gene therapy, cell therapy and immunotherapy
Personalized medicine and pharmacogenomics
Clinical drug evaluation
Patient safety and sustained use of medicines.
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