CASIA OpenIR
Identification of HDAC9 as a viable therapeutic target for the treatment of gastric cancer
Xiong, Kai1,2,3; Zhang, Hejun1,3,4; Du, Yang2,4; Tian, Jie2,5,6; Ding, Shigang1,3
Source PublicationEXPERIMENTAL AND MOLECULAR MEDICINE
ISSN1226-3613
2019-08-26
Volume51Pages:15
Corresponding AuthorDu, Yang(yang.du@ia.ac.cn) ; Tian, Jie(jie.tian@ia.ac.cn) ; Ding, Shigang(dingshigang222@163.com)
AbstractHistone deacetylase inhibitors (HDACis) are a new class of anticancer drugs confirmed to have good therapeutic effects against gastric cancer (GC) in preclinical experiments, but most HDACis are non-selective (pan-HDACis), with highly toxic side effects. Therefore, it is necessary to screen HDAC family members that play key roles in GC as therapeutic targets to reduce toxic side effects. In this study, we evaluated the targeting specificity of the HDACi suberoylanilide hydroxamic acid (SAHA) for GC via fluorescence molecular imaging (FMI). In vitro FMI results showed that SAHA had higher binding affinity for GC cells than for normal gastric cells. In vivo FMI of gastric tumor-bearing mice confirmed that SAHA can be enriched in GC tissues. However, there was also a high-concentration distribution in normal organs such as the stomach and lungs, suggesting potential side effects. In addition, we found that among the HDAC family members, HDAC9 was the most significantly upregulated in GC cells, and we verified this upregulation in GC tissues. Further experiments confirmed that knockdown of HDAC9 inhibits cell growth, reduces colony formation, and induces apoptosis and cell cycle arrest. These results suggest that HDAC9 has an oncogenic role in GC. Moreover, HDAC9 siRNA suppressed GC tumor growth and enhanced the antitumor efficacy of cisplatin in GC treatment by inhibiting the proliferation and inducing the apoptosis of GC cells in vitro and in vivo. Our findings suggest that the development of HDAC9-selective HDACis is a potential approach to improve the efficacy of chemotherapy and reduce systemic toxicity.
DOI10.1038/s12276-019-0301-8
WOS KeywordHISTONE DEACETYLASES ; CELL-PROLIFERATION ; PHASE-II ; EXPRESSION ; COMBINATION ; VORINOSTAT ; CHEMOTHERAPY ; INHIBITION ; PROGNOSIS ; CISPLATIN
Indexed BySCI
Language英语
Funding ProjectNational Key Research and Development Plan of China[2016YFA0201404] ; National Key Research and Development Plan of China[2017YFA0205200] ; National Natural Science Foundation of China[81871514] ; National Natural Science Foundation of China[8187071801] ; National Natural Science Foundation of China[81227901] ; National Natural Science Foundation of China[81470083] ; Strategic Priority Research Program from the Chinese Academy of Sciences[XDB02060010] ; International Innovation Team of CAS[20140491524] ; Beijing Municipal Science & Technology Commission[Z161100002616022]
Funding OrganizationNational Key Research and Development Plan of China ; National Natural Science Foundation of China ; Strategic Priority Research Program from the Chinese Academy of Sciences ; International Innovation Team of CAS ; Beijing Municipal Science & Technology Commission
WOS Research AreaBiochemistry & Molecular Biology ; Research & Experimental Medicine
WOS SubjectBiochemistry & Molecular Biology ; Medicine, Research & Experimental
WOS IDWOS:000482997600001
PublisherNATURE PUBLISHING GROUP
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ia.ac.cn/handle/173211/27273
Collection中国科学院自动化研究所
Corresponding AuthorDu, Yang; Tian, Jie; Ding, Shigang
Affiliation1.Peking Univ, Dept Gastroenterol, Hosp 3, Beijing 100191, Peoples R China
2.Chinese Acad Sci, Inst Automat, CAS Key Lab Mol Imaging, State Key Lab Management & Control Complex Syst, Beijing 100190, Peoples R China
3.Beijing Key Lab Helicobacter Pylori Infect & Uppe, Beijing 100191, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100080, Peoples R China
5.Beihang Univ, Beijing Adv Innovat Ctr Big Data Based Precis Med, Sch Med, Beijing 100191, Peoples R China
6.Xidian Univ, Sch Life Sci & Technol, Engn Res Ctr Mol & Neuro Imaging, Minist Educ, Xian 710126, Shaanxi, Peoples R China
First Author AffilicationInstitute of Automation, Chinese Academy of Sciences
Corresponding Author AffilicationInstitute of Automation, Chinese Academy of Sciences
Recommended Citation
GB/T 7714
Xiong, Kai,Zhang, Hejun,Du, Yang,et al. Identification of HDAC9 as a viable therapeutic target for the treatment of gastric cancer[J]. EXPERIMENTAL AND MOLECULAR MEDICINE,2019,51:15.
APA Xiong, Kai,Zhang, Hejun,Du, Yang,Tian, Jie,&Ding, Shigang.(2019).Identification of HDAC9 as a viable therapeutic target for the treatment of gastric cancer.EXPERIMENTAL AND MOLECULAR MEDICINE,51,15.
MLA Xiong, Kai,et al."Identification of HDAC9 as a viable therapeutic target for the treatment of gastric cancer".EXPERIMENTAL AND MOLECULAR MEDICINE 51(2019):15.
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