Exploring the Molecular Therapeutic Mechanisms of Gemcitabine through Quantitative Proteomics
文献类型：期刊论文
| 作者 | Jiang, Yue8,9; Ren, Xuelian7,8; Zhao, Jing6 ; Liu, Guobin5; Liu, Fangfang4,8; Guo, Xinlong3,4,8; Hao, Ming9; Liu, Hong6; Liu, Kun1,2,9; Huang, He3,4,7,8
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| 刊名 | JOURNAL OF PROTEOME RESEARCH
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| 出版日期 | 2024-06-04 |
| 页码 | 12 |
| 关键词 | gemcitabine pancreatic cancer quantitativeproteomics thermal proteome profiling molecularmechanisms |
| ISSN号 | 1535-3893 |
| DOI | 10.1021/acs.jproteome.3c00890 |
| 通讯作者 | Liu, Kun(kliu@mail.neu.edu.cn) ; Huang, He(hhuang@simm.ac.cn) |
| 英文摘要 | 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. |
| WOS关键词 | BREAST-CANCER ; CELLS ; RESISTANCE ; CISPLATIN ; TARGET ; CHK2 |
| 资助项目 | National Natural Science Foundation of China[22277125] ; National Natural Science Foundation of China[92253306] ; National Natural Science Foundation of China[23ZR1474600] ; Shandong Laboratory Program[SYS202205] ; Shanghai Municipal Science and Technology Major Project ; The 111 Project[B16009] ; Natural Science Foundation of Shenyang City[22-315-6-01] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:001239327200001 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/311585]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Liu, Kun; Huang, He |
| 作者单位 | 1.Northeastern Univ, Key Lab Data Analyt & Optimizat Smart Ind, Minist Educ, Shenyang 110819, Peoples R China 2.Northeastern Univ, Natl Frontiers Sci Ctr Ind Intelligence & Syst Opt, Shenyang 110819, Peoples R China 3.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 7.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China 8.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai 201203, Peoples R China 9.Northeastern Univ, Sch Mech Engn & Automat, Shenyang 110819, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jiang, Yue,Ren, Xuelian,Zhao, Jing,et al. Exploring the Molecular Therapeutic Mechanisms of Gemcitabine through Quantitative Proteomics[J]. JOURNAL OF PROTEOME RESEARCH,2024:12. |
| APA | Jiang, Yue.,Ren, Xuelian.,Zhao, Jing.,Liu, Guobin.,Liu, Fangfang.,...&Huang, He.(2024).Exploring the Molecular Therapeutic Mechanisms of Gemcitabine through Quantitative Proteomics.JOURNAL OF PROTEOME RESEARCH,12. |
| MLA | Jiang, Yue,et al."Exploring the Molecular Therapeutic Mechanisms of Gemcitabine through Quantitative Proteomics".JOURNAL OF PROTEOME RESEARCH (2024):12. |
入库方式： OAI收割
来源：上海药物研究所
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