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10.1371/journal.pone.0156643

http://scihub22266oqcxt.onion/10.1371/journal.pone.0156643
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suck abstract from ncbi


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pmid27284967
      PLoS+One 2016 ; 11 (6 ): e0156643
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  • Epirubicin, Identified Using a Novel Luciferase Reporter Assay for Foxp3 Inhibitors, Inhibits Regulatory T Cell Activity #MMPMID27284967
  • Kashima H ; Momose F ; Umehara H ; Miyoshi N ; Ogo N ; Muraoka D ; Shiku H ; Harada N ; Asai A
  • PLoS One 2016[]; 11 (6 ): e0156643 PMID27284967 show ga
  • Forkhead box protein p3 (Foxp3) is crucial to the development and suppressor function of regulatory T cells (Tregs) that have a significant role in tumor-associated immune suppression. Development of small molecule inhibitors of Foxp3 function is therefore considered a promising strategy to enhance anti-tumor immunity. In this study, we developed a novel cell-based assay system in which the NF-?B luciferase reporter signal is suppressed by the co-expressed Foxp3 protein. Using this system, we screened our chemical library consisting of approximately 2,100 compounds and discovered that a cancer chemotherapeutic drug epirubicin restored the Foxp3-inhibited NF-?B activity in a concentration-dependent manner without influencing cell viability. Using immunoprecipitation assay in a Treg-like cell line Karpas-299, we found that epirubicin inhibited the interaction between Foxp3 and p65. In addition, epirubicin inhibited the suppressor function of murine Tregs and thereby improved effector T cell stimulation in vitro. Administration of low dose epirubicin into tumor-bearing mice modulated the function of immune cells at the tumor site and promoted their IFN-? production without direct cytotoxicity. In summary, we identified the novel action of epirubicin as a Foxp3 inhibitor using a newly established luciferase-based cellular screen. Our work also demonstrated our screen system is useful in accelerating discovery of Foxp3 inhibitors.
  • |*Genes, Reporter [MESH]
  • |*Luciferases/genetics/metabolism [MESH]
  • |Animals [MESH]
  • |Antineoplastic Agents/*isolation & purification/pharmacology [MESH]
  • |Cells, Cultured [MESH]
  • |Down-Regulation/drug effects [MESH]
  • |Drug Screening Assays, Antitumor/*methods [MESH]
  • |Epirubicin/*isolation & purification/pharmacology [MESH]
  • |Female [MESH]
  • |Forkhead Transcription Factors/*antagonists & inhibitors [MESH]
  • |HEK293 Cells [MESH]
  • |Humans [MESH]
  • |Lymphocyte Activation/drug effects [MESH]
  • |Mice [MESH]
  • |Mice, Inbred BALB C [MESH]


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