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An Integrative Proteome-Based Pharmacologic Characterization and Therapeutic Strategy Exploration of SAHA in Solid Malignancies br

文献类型：期刊论文

作者Liu, Quan1,2; Hao, Bingbing2; Zhang, Mingya3; Liu, Zhiwei1,2; Huang, Yuqi1,2; Zhao, Xiaoxiao3; Hu, Hao2; Tan, Minjia1,2,3; Xu, Jun-Yu1,2
刊名JOURNAL OF PROTEOME RESEARCH
出版日期2022-04-01
卷号21期号:4页码:953-964
ISSN号1535-3893
关键词proteomics SAHA 2-deoxy-D-glucose new combination strategy
DOI10.1021/acs.jproteome.1c00791
通讯作者Tan, Minjia(mjtan@simm.ac.cn) ; Xu, Jun-Yu(jyxu@simm.ac.cn)
英文摘要Targeting histone epigenetic modification is an important strategy foranticancer therapy. Histone deacetylase inhibitors (HDACis) have been clinicallyapproved in the treatment of diverse hematological cancers, but mechanisms of drugresistance and poor therapeutic efficacy in solid malignancies remain largelyunknown. In this study, we applied a mass spectrometry-based quantitative proteomicstrategy to investigate the molecular differences in HDACi vorinostat (SAHA)sensitive and resistant cell lines. The proteomic results revealed that the glycolysispathway was highly enriched after vorinostat treatment in the resistant cell line,leading to the prediction of a new drug combination, SAHA and hexokinase inhibitor(2-deoxyglucose). The efficacy of this combination was further verified in severalsolid tumor cell lines. Quantitative proteomics revealed that alterations in thetranscription process and protein homeostasis could play roles in the synergeticutilization of these two compounds. Our study showed the application of proteomicsin elucidating the drug mechanism and predicting drug combination and the potentialof expanding the utilization of HDACi
WOS关键词CONNECTIVITY MAP ; GENE-EXPRESSION ; CANCER ; INHIBITORS ; ACETYLATION ; SENSITIVITY ; COMBINATION ; METABOLISM ; LANDSCAPE ; DISCOVERY
资助项目National Key R&D Program of China[2020YFE0202200] ; National Key R&D Program of China[2021YFA0804700] ; National Key R&D Program of China[2021YFA0804701] ; Natural Science Foundation of China[81821005] ; Natural Science Foundation of China[81872888] ; Natural Science Foundation of China[31901036] ; Natural Science Foundation of China[32071432] ; Natural Science Foundation of China[91853126] ; Shanghai Sailing Program[19YF1457700] ; Youth Innovation Promotion Association CAS ; SA-SIBS Scholarship Program
WOS研究方向Biochemistry & Molecular Biology
语种英语
出版者AMER CHEMICAL SOC
WOS记录号WOS:000784194300010
源URL[http://119.78.100.183/handle/2S10ELR8/299545]  
专题新药研究国家重点实验室
通讯作者Tan, Minjia; Xu, Jun-Yu
作者单位1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
推荐引用方式
GB/T 7714		 Liu, Quan,Hao, Bingbing,Zhang, Mingya,et al. An Integrative Proteome-Based Pharmacologic Characterization and Therapeutic Strategy Exploration of SAHA in Solid Malignancies br[J]. JOURNAL OF PROTEOME RESEARCH,2022,21(4):953-964.
APA Liu, Quan.,Hao, Bingbing.,Zhang, Mingya.,Liu, Zhiwei.,Huang, Yuqi.,...&Xu, Jun-Yu.(2022).An Integrative Proteome-Based Pharmacologic Characterization and Therapeutic Strategy Exploration of SAHA in Solid Malignancies br.JOURNAL OF PROTEOME RESEARCH,21(4),953-964.
MLA Liu, Quan,et al."An Integrative Proteome-Based Pharmacologic Characterization and Therapeutic Strategy Exploration of SAHA in Solid Malignancies br".JOURNAL OF PROTEOME RESEARCH 21.4(2022):953-964.

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来源：上海药物研究所

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