Green tea polyphenol epigallocatechin-3-gallate blocks PDGF-induced proliferation and migration of rat pancreatic stellate cells

Aim: To clarify the effects of epigallocatechin-3-gallate (EGCG) on the platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of pancreatic stellate cells (PSCs). Methods: PSCs were isolated from rat pancreas tissue and used in their culture-activated, myofibroblast-like phenotype. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2′-deoxyuridine. Cell migration was assessed using modified Boyden chambers. Cyclin D1, p21^Waf1, and p27^Kip1 expression and phosphorylation of PDGF β-receptor, extracellular signal-regulated kinase, and Akt were examined by Western blotting. Activation of phosphatidylinositol 3-kinase was examined by kinase assay using phosphatidylinositol as a substrate. Cell cycle was assessed by flow cytometry after staining with propidium iodide. Results: EGCG at non-cytotoxic concentrations inhibited PDGF-induced proliferation and migration. This effect was associated with the inhibition of cell cycle progression beyond the G₁ phase, decreased cyclin D1 and increased p27^Kip1 expression. EGCG inhibited tyrosine phosphorylation of PDGF β-receptor and downstream activation of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase/Akt pathways. Conclusion: EGCG inhibited PDGF-BB-induced proliferation and migration of PSCs through the inhibition of PDGF-mediated signaling pathways.