{"title":"嘧菌酯通过调节 HIF1A 抑制卵巢癌细胞中的糖酵解作用","authors":"Yi Yang, Huimin Wang, Qiong Wei, Chun Li","doi":"10.1016/j.mrfmmm.2024.111884","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Ovarian cancer is one of the most common tumors affecting females, significantly disrupting their quality of life. Agrimonolide, an extract derived from Agrimony (<em>Agrimonia pilosa</em> Ledeb.), has been shown to exert various regulatory effects on several diseases. Notably, recent studies indicate that Agrimonolide may attenuate the progression of ovarian cancer. However, the detailed regulatory mechanisms of Agrimonolide in this context require further investigation.</div></div><div><h3>Purpose</h3><div>To determine the significance of HIF1A as a key target in ovarian cancer and its potential underlying signaling pathway.</div></div><div><h3>Methods</h3><div>Cell viability and proliferation were assessed using CCK-8 and colony formation assays. Glucose uptake and lactate production were measured using commercial kits, and the extracellular acidification rate (ECAR) was evaluated. Protein expression levels were analyzed through western blotting.</div></div><div><h3>Results</h3><div>Our network pharmacology analysis identified HIF1A as a crucial target and signaling pathway in ovarian cancer. Furthermore, treatment with Agrimonolide (20 μM and 40 μM) inhibited the growth of ovarian cancer cells. Agrimonolide also reduced glycolytic activity in these cells. Additionally, Agrimonolide treatment led to decreased expression levels of HIF1A, HK2, and LDHA in ovarian cancer cells. Rescue assays revealed that glucose uptake and lactate production were diminished following Agrimonolide treatment; however, these effects were reversed upon overexpression of HIF1A.</div></div><div><h3>Conclusion</h3><div>This study showed that Agrimonolide can suppress glycolysis in ovarian cancer cells by modulating HIF1A, supporting Agrimonolide as a promising therapeutic agent for ovarian cancer treatment.</div></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"829 ","pages":"Article 111884"},"PeriodicalIF":1.5000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Agrimonolide inhibits glycolysis in ovarian cancer cells by regulating HIF1A\",\"authors\":\"Yi Yang, Huimin Wang, Qiong Wei, Chun Li\",\"doi\":\"10.1016/j.mrfmmm.2024.111884\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Ovarian cancer is one of the most common tumors affecting females, significantly disrupting their quality of life. Agrimonolide, an extract derived from Agrimony (<em>Agrimonia pilosa</em> Ledeb.), has been shown to exert various regulatory effects on several diseases. Notably, recent studies indicate that Agrimonolide may attenuate the progression of ovarian cancer. However, the detailed regulatory mechanisms of Agrimonolide in this context require further investigation.</div></div><div><h3>Purpose</h3><div>To determine the significance of HIF1A as a key target in ovarian cancer and its potential underlying signaling pathway.</div></div><div><h3>Methods</h3><div>Cell viability and proliferation were assessed using CCK-8 and colony formation assays. Glucose uptake and lactate production were measured using commercial kits, and the extracellular acidification rate (ECAR) was evaluated. Protein expression levels were analyzed through western blotting.</div></div><div><h3>Results</h3><div>Our network pharmacology analysis identified HIF1A as a crucial target and signaling pathway in ovarian cancer. Furthermore, treatment with Agrimonolide (20 μM and 40 μM) inhibited the growth of ovarian cancer cells. Agrimonolide also reduced glycolytic activity in these cells. Additionally, Agrimonolide treatment led to decreased expression levels of HIF1A, HK2, and LDHA in ovarian cancer cells. Rescue assays revealed that glucose uptake and lactate production were diminished following Agrimonolide treatment; however, these effects were reversed upon overexpression of HIF1A.</div></div><div><h3>Conclusion</h3><div>This study showed that Agrimonolide can suppress glycolysis in ovarian cancer cells by modulating HIF1A, supporting Agrimonolide as a promising therapeutic agent for ovarian cancer treatment.</div></div>\",\"PeriodicalId\":49790,\"journal\":{\"name\":\"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis\",\"volume\":\"829 \",\"pages\":\"Article 111884\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2024-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0027510724000344\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0027510724000344","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
Agrimonolide inhibits glycolysis in ovarian cancer cells by regulating HIF1A
Background
Ovarian cancer is one of the most common tumors affecting females, significantly disrupting their quality of life. Agrimonolide, an extract derived from Agrimony (Agrimonia pilosa Ledeb.), has been shown to exert various regulatory effects on several diseases. Notably, recent studies indicate that Agrimonolide may attenuate the progression of ovarian cancer. However, the detailed regulatory mechanisms of Agrimonolide in this context require further investigation.
Purpose
To determine the significance of HIF1A as a key target in ovarian cancer and its potential underlying signaling pathway.
Methods
Cell viability and proliferation were assessed using CCK-8 and colony formation assays. Glucose uptake and lactate production were measured using commercial kits, and the extracellular acidification rate (ECAR) was evaluated. Protein expression levels were analyzed through western blotting.
Results
Our network pharmacology analysis identified HIF1A as a crucial target and signaling pathway in ovarian cancer. Furthermore, treatment with Agrimonolide (20 μM and 40 μM) inhibited the growth of ovarian cancer cells. Agrimonolide also reduced glycolytic activity in these cells. Additionally, Agrimonolide treatment led to decreased expression levels of HIF1A, HK2, and LDHA in ovarian cancer cells. Rescue assays revealed that glucose uptake and lactate production were diminished following Agrimonolide treatment; however, these effects were reversed upon overexpression of HIF1A.
Conclusion
This study showed that Agrimonolide can suppress glycolysis in ovarian cancer cells by modulating HIF1A, supporting Agrimonolide as a promising therapeutic agent for ovarian cancer treatment.
期刊介绍：
Mutation Research (MR) provides a platform for publishing all aspects of DNA mutations and epimutations, from basic evolutionary aspects to translational applications in genetic and epigenetic diagnostics and therapy. Mutations are defined as all possible alterations in DNA sequence and sequence organization, from point mutations to genome structural variation, chromosomal aberrations and aneuploidy. Epimutations are defined as alterations in the epigenome, i.e., changes in DNA methylation, histone modification and small regulatory RNAs.
MR publishes articles in the following areas:
Of special interest are basic mechanisms through which DNA damage and mutations impact development and differentiation, stem cell biology and cell fate in general, including various forms of cell death and cellular senescence.
The study of genome instability in human molecular epidemiology and in relation to complex phenotypes, such as human disease, is considered a growing area of importance.
Mechanisms of (epi)mutation induction, for example, during DNA repair, replication or recombination; novel methods of (epi)mutation detection, with a focus on ultra-high-throughput sequencing.
Landscape of somatic mutations and epimutations in cancer and aging.
Role of de novo mutations in human disease and aging; mutations in population genomics.
Interactions between mutations and epimutations.
The role of epimutations in chromatin structure and function.
Mitochondrial DNA mutations and their consequences in terms of human disease and aging.
Novel ways to generate mutations and epimutations in cell lines and animal models.
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