Yue Jiang, Xuelian Ren, Jing Zhao, Guobin Liu, Fangfang Liu, Xinlong Guo, Ming Hao, Hong Liu, Kun Liu* and He Huang*,
{"title":"Exploring the Molecular Therapeutic Mechanisms of Gemcitabine through Quantitative Proteomics","authors":"Yue Jiang, Xuelian Ren, Jing Zhao, Guobin Liu, Fangfang Liu, Xinlong Guo, Ming Hao, Hong Liu, Kun Liu* and He Huang*, ","doi":"10.1021/acs.jproteome.3c00890","DOIUrl":null,"url":null,"abstract":"<p >Gemcitabine (GEM) is widely employed in the treatment of various cancers, including pancreatic cancer. Despite their clinical success, challenges related to GEM resistance and toxicity persist. Therefore, a deeper understanding of its intracellular mechanisms and potential targets is urgently needed. In this study, through mass spectrometry analysis in data-dependent acquisition mode, we carried out quantitative proteomics (three independent replications) and thermal proteome profiling (TPP, two independent replications) on MIA PaCa-2 cells to explore the effects of GEM. Our proteomic analysis revealed that GEM led to the upregulation of the cell cycle and DNA replication proteins. Notably, we observed the upregulation of S-phase kinase-associated protein 2 (SKP2), a cell cycle and chemoresistance regulator. Combining SKP2 inhibition with GEM showed synergistic effects, suggesting SKP2 as a potential target for enhancing the GEM sensitivity. Through TPP, we pinpointed four potential GEM binding targets implicated in tumor development, including in breast and liver cancers, underscoring GEM’s broad-spectrum antitumor capabilities. These findings provide valuable insights into GEM’s molecular mechanisms and offer potential targets for improving treatment efficacy.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8000,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Proteome Research","FirstCategoryId":"99","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.jproteome.3c00890","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0
Abstract
Gemcitabine (GEM) is widely employed in the treatment of various cancers, including pancreatic cancer. Despite their clinical success, challenges related to GEM resistance and toxicity persist. Therefore, a deeper understanding of its intracellular mechanisms and potential targets is urgently needed. In this study, through mass spectrometry analysis in data-dependent acquisition mode, we carried out quantitative proteomics (three independent replications) and thermal proteome profiling (TPP, two independent replications) on MIA PaCa-2 cells to explore the effects of GEM. Our proteomic analysis revealed that GEM led to the upregulation of the cell cycle and DNA replication proteins. Notably, we observed the upregulation of S-phase kinase-associated protein 2 (SKP2), a cell cycle and chemoresistance regulator. Combining SKP2 inhibition with GEM showed synergistic effects, suggesting SKP2 as a potential target for enhancing the GEM sensitivity. Through TPP, we pinpointed four potential GEM binding targets implicated in tumor development, including in breast and liver cancers, underscoring GEM’s broad-spectrum antitumor capabilities. These findings provide valuable insights into GEM’s molecular mechanisms and offer potential targets for improving treatment efficacy.
期刊介绍:
Journal of Proteome Research publishes content encompassing all aspects of global protein analysis and function, including the dynamic aspects of genomics, spatio-temporal proteomics, metabonomics and metabolomics, clinical and agricultural proteomics, as well as advances in methodology including bioinformatics. The theme and emphasis is on a multidisciplinary approach to the life sciences through the synergy between the different types of "omics".