Background Pancreatic cancer is a devastating disease with the worst mortality rate.Therefore,a rational strategy for future drug development is critical.Genistein is a small,biologically active flavonoid that is found in high amounts in soy.This important compound supports a wide variety of biological activities,but is best known for its ability to inhibit cancer progression.Methods Transwell chamber assay was performed to determine the effect of genistein on the invasion of the human pancreatic cancer cell line Panc-1 induced by transforming growth factor-β1 (TGF-β1) in the different condition (5 ng/ml 24 hours and 10 ng/ml 48 hours); Reverse transcription-polymerase chain reaction (RT-PCR) was used to estimate the mRNA levels of urinary plasminogen activator (uPA),matrix metallopeptidase 2/9 (MMP-2/9),Smad4,E-Cadherin and Vimentin; West blotting was used to detect the protein levels of uPA,E-Cadherin,ERK1/2,P38 and P-P38,and the activity of MMP-2/9 protein were detected by gelatin zymography assay method.Cells structure was observed and analyzed by microscopy.Results Genistein can inhibit effectively TGF-β1-induced invasion and metastasis in Panc-1 by Transwell assay,which is through regulating the mRNA and protein expression of uPA and MMP2,but not MMP9 by RT-PCR / West blotting,and is positively correlated with the concentration of genistein.At the same time,genistein also could improve the progress of epithelial-mesenchymal transition (EMT) via morphology observation using light microscopy / transmission electron microscopy (TEM),which is mediated by the down-regulation of E-cadherin and the up-regulation of vimentin.Conclusions TGF-β1 mediates EMT process via numerous intracellular signal transduction pathways.The potential molecular mechanisms are all or partly through Smad4-dependent and -independent pathways (p38 MAPK) to regulate the antitumor effect of genistein.