title: In vitro anti-angiogenic properties of LGD1069, a selective retinoid X-receptor agonist through down-regulating Runx2 expression on Human endothelial cells.
abstract: BACKGROUND
  LGD1069 (Targretin®) is a selective retinoid X receptor (RXR) ligand, which is used in patients for cutaneous T-cell lymphoma. Our published study reported that LGD1069 inhibited tumor-induced angiogenesis in non-small cell lung cancer. In present study, we found that LGD1069 suppressed the proliferation, adhesion, invasion and migration of endothelial cells directly, and affected the expression of vegf and some matrix genes.
  
  
  METHODS
  Human umbilical vein endothelial cells (HUVECs) were used for in vitro study. MTT assay and Sulforhodamine B assay were used for cell viability assay; the tube formation assay was used to investigate the effect of LGD1069 on angiogenesis in vitro. In vitro adhesion, migration and invasion of HUVEC cells were analyzed by Matrigel adhesion, migration and invasion assay. Gene expressions were measured by RT-PCR and Western blot analysis.
  
  
  RESULTS
  Our data showed here that LGD1069 inhibited the activation of TGF-β/Smad pathway significantly. Furthermore, it was demonstrated that expression of Runx2 was suppressed pronouncedly during incubation with LGD1069. Runx2 is a DNA-binding transcription factor which plays a master role in tumor-induced angiogenesis and cancer cells metastasis by interaction with the TGF-β/Smad pathway of transcriptional modulators.
  
  
  CONCLUSIONS
  Our results suggested that LGD1069 may impair angiogenic and metastatic potential induced by tumor cells through suppressing expression of Runx2 directly on human endothelial cells, which may point out new pathway through which LGD1069 display anti-angiogenic properties, and provide new molecular evidence to support LGD1069 as a potent anti-metastatic agent in cancer therapy.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004 China. jianjiang.fu@gmail.com
authors.forename: Jianjiang
authors.initials: J
authors.lastname: Fu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.forename: Yongming
authors.initials: Y
authors.lastname: Luo
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000077610:Bexarotene; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D047488:Retinoid X Receptors / Q000819:agonists*; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
chemical_list: D020533:Angiogenesis Inhibitors; D050659:Core Binding Factor Alpha 1 Subunit; D047488:Retinoid X Receptors; D051899:Smad2 Protein; D051900:Smad3 Protein; D013764:Tetrahydronaphthalenes; D000077610:Bexarotene; D020782:Matrix Metalloproteinases