In vitro anti-angiogenic properties of LGD1069, a selective retinoid X-receptor agonist through down-regulating Runx2 expression on Human endothelial cells

BMC Cancer

Yongming Luo²  Hong Lu¹  Yu-Hui Liu²  Wei Wang²  Jianjiang Fu² 

[1]Modern Education Technology Center, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004 China

[2]Department of Pharmacology, College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004 China

关键词: Runx2;    angiogenesis;    metastasis;    retinoid X receptor;    LGD1069;   

Others  :  1080908
DOI  :  10.1186/1471-2407-11-227

 received in 2010-10-11, accepted in 2011-06-07,  发布年份 2011

【 摘 要 】

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.

【 授权许可】

   
2011 Fu et al; licensee BioMed Central Ltd.

【 图 表 】

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