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Epigenetic targeting drugs potentiate chemotherapeutic effects in solid tumor therapy
Li, Jingjing1; Hao, Dapeng1; Wang, Li1,2; Wang, Haitao1; Wang, Yuan1; Zhao, Zhiqiang1; Li, Peipei1; Deng, Chuxia1; Di, Li-Jun1
2017-06-22
Source PublicationSCIENTIFIC REPORTS
ISSN2045-2322
Volume7
Abstract

Epigenetic therapy is a novel tumor therapeutic method and refers to the targeting of the aberrant epigenetic modifications presumably at cancer-related genes by chemicals which are epigenetic targeting drugs (ETDs). Not like in treating hematopoietic cancer, the clinical trials investigating the potential use of ETDs in the solid tumor is not encouraging. Instead, the curative effects of ETD delivered together with DNA targeting chemo drugs (DTDs) are quite promising according to our metaanalysis. To investigate the synergistic mechanism of ETD and DTD drug combination, the therapeutic effect was studied using both cell lines and mouse engrafted tumors. Mechanically we show that HDAC inhibitors and DNMT inhibitors are capable of increasing the chromatin accessibility to cisplatin (CP) and doxorubicin (Dox) through chromatin decompaction globally. Consequently, the combination of ETD and DTD enhances the DTD induced DNA damage and cell death. Engrafted tumors in SCID mice also show increased sensitivity to irradiation (IR) or CP when the tumors were pretreated by ETDs. Given the limited therapeutic effect of ETD alone, these results strongly suggest that the combination of DTD, including irradiation, and ETD treatment is a very promising choice in clinical solid tumor therapy.

DOIhttp://doi.org/10.1038/s41598-017-04406-0
URLView the original
Indexed BySCI
Language英语
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000403874900018
PublisherNATURE PUBLISHING GROUP
The Source to ArticleWOS
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Cited Times [WOS]:11   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorDi, Li-Jun
Affiliation1.Cancer Center, Faculty of Health Sciences, University of Macau, Macau, China
2.Metabolomics Core, Faculty of Health Sciences, University of Macau, Macau, China
First Author AffilicationFaculty of Health Sciences
Corresponding Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Li, Jingjing,Hao, Dapeng,Wang, Li,et al. Epigenetic targeting drugs potentiate chemotherapeutic effects in solid tumor therapy[J]. SCIENTIFIC REPORTS,2017,7.
APA Li, Jingjing.,Hao, Dapeng.,Wang, Li.,Wang, Haitao.,Wang, Yuan.,...&Di, Li-Jun.(2017).Epigenetic targeting drugs potentiate chemotherapeutic effects in solid tumor therapy.SCIENTIFIC REPORTS,7.
MLA Li, Jingjing,et al."Epigenetic targeting drugs potentiate chemotherapeutic effects in solid tumor therapy".SCIENTIFIC REPORTS 7(2017).
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