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

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.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.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.Carcinomas are the most frequent type of human malignancies, and the vast majority of cancer deaths are caused by the formation of metastases rather than by the primary tumor itself [1]. Despite its clinical importance, spreading to distant organs remains the most insidious aspect of solid cancers, and the complexities about the genetic and biochemical determinants remain poorly understood. But for more than a century, cancer biologists paid lots of attention to this aspect. Based on current findings in this field, Gupta et al. posed a framework of cancer metastasis. There are several key steps in the biological cascade of metastasis: altered cellular adhesion and cell motility, disruption of the basement membrane and extracellular matrix, entry and survival