2-furoyl-ligrlo-amide and Colonic-Neoplasms

Tissue factor (TF)/VIIa/protease‑activated receptor 2 (PAR2) has been shown to trigger the ERK1/2 signaling pathway. This was shown to be closely associated with the proliferation and migration of SW620 colon cancer cells; however, the detailed mechanisms remain unclear. The aim of the present study was to elucidate the effects of calcium signaling on the proliferation and migration of SW620 cells induced by coagulation factor VIIa. The results demonstrated that VIIa and PAR2 agonist PAR2‑AP increased [Ca2+]i in SW620 cells. In addition, VIIa‑and PAR2‑AP‑induced ERK1/2 activation was inhibited by thapsigargin (TG)‑induced depletion of intracellular Ca2+ stores and EGTA‑mediated removal of extracellular Ca2+. It was also identified that VIIa and PAR2‑AP‑induced proliferation and migration of SW620 cells was modulated by EGTA and TG. Taken together, the present results indicate that VIIa triggers calcium signaling in SW620 cells, in a TF‑dependent manner, which is critical for VIIa‑induced ERK1/2 activation in SW620 cells. These results suggested that calcium signaling had a vital role in the proliferation and migration of SW620 cells.

Topics: Calcium; Calcium Signaling; Cell Line, Tumor; Cell Movement; Cell Proliferation; Colonic Neoplasms; Factor VIIa; Humans; MAP Kinase Signaling System; Oligopeptides; Receptor, PAR-2; Signal Transduction

Epigallocatechin-3-gallate (EGCG) is the major polyphenolic constituent in green tea. The aim of this study is to investigate the effects of EGCG on proliferation and migration of the human colon cancer SW620 cells.. Proliferation and migration of SW620 cells were induced by the protease-activated receptor 2-agonist peptide (PAR2-AP, 100 μmol/L) or factor VIIa (10 nmol/L), and analyzed using MTT and Transwell assays, respectively. The cellular cytoskeleton was stained with rhodamine-conjugated phalloidin and examined with a laser scanning confocal fluorescence microscope. The expression of caspase-7, tissue factor (TF) and matrix metalloproteinase (MMP)-9 in the cells was examined using QT-PCR, ELISA and Western blot assays. The activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and nuclear factor-kappa B (NF-κB) signaling pathways was analyzed with Western blot.. Both PAR2-AP and factor VIIa promoted SW620 cell proliferation and migration, and caused cytoskeleton reorganization (increased filopodia and pseudopodia). Pretreatment with EGCG (25, 50, 75, and 100 μg/mL) dose-dependently blocked the cell proliferation and migration induced by PAR2-AP or factor VIIa. EGCG (100 μg/mL) prevented the cytoskeleton changes induced by PAR2-AP or factor VIIa. EGCG (100 μg/mL) counteracted the down-regulation of caspase-7 expression and up-regulation of TF and MMP-9 expression in the cells treated with PAR2-AP or factor VIIa. Furthermore, it blocked the activation of ERK1/2 and NF-κB (p65/RelA) induced by PAR2-AP or factor VIIa.. EGCG blocks the proliferation and migration of SW620 cells induced by PAR2-AP and factor VIIa via inhibition of the ERK1/2 and NF-κB pathways. The compound may serve as a preventive and therapeutic agent for colon cancers.

Topics: Anticarcinogenic Agents; Caspase 7; Catechin; Cell Line, Tumor; Cell Movement; Cell Proliferation; Colonic Neoplasms; Cytoskeleton; Extracellular Signal-Regulated MAP Kinases; Factor VIIa; Humans; MAP Kinase Signaling System; Matrix Metalloproteinase 9; NF-kappa B; Oligopeptides; Receptor, PAR-2; Signal Transduction