Angiogenesis In Cell Lines Research Articles

Transcription Factor Prospero Homeobox 1 (PROX1) as a Potential Angiogenic Regulator of Follicular Thyroid Cancer Dissemination.

It is well known that Prospero homeobox 1 (PROX1) is a crucial regulator of lymphangiogenesis, that reprograms blood endothelial cells to lymphatic phenotype. However, the role of PROX1 in tumor progression, especially in angiogenesis remains controversial. Herein, we studied the role of PROX1 in angiogenesis in cell lines derived from follicular thyroid cancer (FTC: FTC-133) and squamous cell carcinoma of the thyroid gland (SCT: CGTH-W-1) upon PROX1 knockdown. The genes involved in angiogenesis were selected by RNA-seq, and the impact of PROX1 on vascularization potential was investigated using human umbilical vein endothelial cells (HUVECs) cultured in conditioned medium collected from FTC- or SCT-derived cancer cell lines after PROX1 silencing. The angiogenic phenotype was examined in connection with the analysis of focal adhesion and correlated with fibroblast growth factor 2 (FGF2) levels. Additionally, the expression of selected genes involved in angiogenesis was detected in human FTC tissues. As a result, we demonstrated that PROX1 knockdown resulted in upregulation of factors associated with vascularization, such as metalloproteinases (MMP1 and 3), FGF2, vascular endothelial growth factors C (VEGFC), BAI1 associated protein 2 (BAIAP2), nudix hydrolase 6 (NUDT6), angiopoietin 1 (ANGPT1), and vascular endothelial growth factor receptor 2 (KDR). The observed molecular changes resulted in the enhanced formation of capillary-like structures by HUVECs and upregulated focal adhesion in FTC-133 and CGTH-W-1 cells. The signature of selected angiogenic genes’ expression in a series of FTC specimens varied depending on the case. Interestingly, PROX1 and FGF2 showed opposing expression levels in FTC tissues and seven thyroid tumor-derived cell lines. In summary, our data revealed that PROX1 is involved in the spreading of thyroid cancer cells by regulation of angiogenesis.

Novel synthetic curcumin analogs as potent antiangiogenic agents in colorectal cancer.

The transcription factor NF-κB plays a central role in angiogenesis in colorectal cancer (CRC). Curcumin is a natural dietary product that inhibits NF-κB. The objective of this study is to evaluate the antiangiogenic effects of curcumin and two potent synthetic analogues (EF31 and UBS109) in CRC. IC50 values for curcumin, EF31, and UBS109 were determined in the HCT116 and HT-29 cell lines. HUVEC tube formation, egg CAM assay, and matrigel plug assays revealed decreased angiogenesis in cell lines treated with curcumin, EF31, or UBS109. Curcumin and its analogues significantly inhibited VEGF-A synthesis and secretion in both cell lines in association with loss of HIF-1α, COX-2, and p-STAT-3 expression. Nuclear NF-κB expression was inhibited by curcumin, EF31, and UBS109. Transfection of p65-NF-κB in HCT116 and HT-29 cells resulted in increased expression of HIF-1α, COX-2, STAT-3, and VEGF-A. Treatment with curcumin, EF31, or UBS109 inhibited these effects in transfected cell lines. In mice carrying HCT116 and HT-29 cell xenografts, EF31 and UBS109 inhibited subcutaneous tumor growth and potentiated the effects of oxaliplatin and 5-FU. Tumors from treated animals revealed inhibition of HIF-1α, COX-2, p-STAT-3, and VEGF expression. Our findings suggest that inhibition of NF-κB leading to decreased transcription and expression of HIF-1α, COX-2, STAT-3, and VEGF is a rational approach for antiangiogenic therapy in CRC. The distinctive properties of EF31 and UBS109 make them promising therapeutic agents for development in CRC as single agents or as part of combination chemotherapy regimens. © 2016 Wiley Periodicals, Inc.