The synergistic effects of notch-1, IL-1β and leptin on migration and angiogenesis in colorectal cancer

Purpose: The aim of this study was to investigate the synergistic interaction of Notch-1, interleukin-1 beta, and leptin on each other, cell migration, and proangiogenic signaling in colorectal cancer cell lines.Materials and Methods: Human colorectal cancer cell lines, HCT-116 and HCT-15, were used. The genes for Notch-1, interleukin-1 beta, and leptin were silenced using small interfering ribonucleic acid. The efficacy of gene silencing and the messenger ribonucleic acid levels of target genes, including Notch-1, interleukin-1 beta, interleukin-1 receptor, leptin, vascular endothelial growth factor A, vascular endothelial growth factor receptor 2, and matrix metalloproteinase-2, were analyzed via quantitative real-time polymerase chain reaction. Protein levels of interleukin-1 beta, leptin, and vascular endothelial growth factor A were also measured using enzyme-linked immunosorbent assay.Results: In the Notch-1 inhibition group, significant decreases were observed in the messenger ribonucleic acid levels of Notch-1, interleukin-1 beta, interleukin-1 receptor (a 3.45-fold decrease), leptin, vascular endothelial growth factor receptor 2, and matrix metalloproteinase-2 (a 6.36-fold decrease). Leptin inhibition led to reduced messenger ribonucleic acid levels of Notch-1, interleukin-1 beta (a 3.67-fold decrease), interleukin-1 receptor (a 2.53-fold decrease), leptin, vascular endothelial growth factor A, and matrix metalloproteinase-2 (a 3.22-fold decrease). Conclusion: Notch-1, interleukin-1 beta, and leptin interact with each other, directly contributing to cell migration and the expression of angiogenic molecules in colorectal cancer.