Aromatic Hydrocarbon Receptor Suppresses Prostate Cancer Bone Metastasis Cells-Induced Vasculogenesis of Endothelial Progenitor Cells under Hypoxia.

摘要: Background/Aims: Hypoxia leads to the development of neovascularization in solid tumor by regulating VEGF expression. Aromatic hydrocarbon receptor (AHR), a for dioxin-like compounds, functions as transcription factor through dimerization with hypoxia-inducible factors 1β (HIF-1β) and inhibits secretion vascular endothelial growth (VEGF). The purpose this study was explore whether AHR can suppress hypoxia-induced production prostate bone metastasis cells repress progenitor (EPCs), and, if so, what mechanisms. Methods: PC-3 or LNCaP induced angiogenesis detected Matrigel-based tube formation assay, mRNA expression levels measured qRT-PCR, level determined ELISA respectively. Results: activation adhesiveness vasculogenesis EPCs under hypoxia. Moreover, suppressed (48 ± 14% PC-3, p = 0.000; 41 LNCaP, 0.000) attenuating HIF-1α HIF-1β that turn diminished angiogenic ability vitro. Furthermore, we found 1α (HIF-1α) (1.54 0.13 fold 0.002, 1.62 0.12 0.001) (1.67 0.23 0.007; 1.75 0.26 p=0.008) were upregulated cancer cell lines response hypoxia, revealed regulation possibly mediated phosphatidylinositol 3-kinase pathway. Conclusion: By providing mechanistic insight into modulation ligand, suggest ligand has strong potential being new therapeutic agent applications field metastatic cancer.