DADS inhibits human colorectal cancer SW480 cell invasion and EMT by negatively regula-ting uPA/uPAR signaling pathway
Aim To explore the possible mechanism of diallyl disulfide(DADS)to inhibit invasion and epithelial-mesen-chymal transition(EMT)of human colorectal cancer SW480 cells.Methods The expression of urokinase-type plasminogen acti-vator(uPA)receptor(uPAR)in colon cancer tissues was detected by immunohistochemistry.uPAR overexpressing cells were con-structed by gene transfection.The experiment was divided into SW480 group,SW480+DADS group,uPAR group,uPAR+DADS group.The cell migration and invasion ability in each group were detected through migration and invasion tests.The expression of mRAN and its protein in related signaling pathways was detected by RT-PCR and Western blotting.Nude mouse experiments were conducted to verify the effect of DADS on uPAR overexpressing SW480 cell transplantation tumors.Results The expression of uPAR in colon cancer tissues was significantly higher than that in adjacent normal tissues(P＜0.05).SW480 cells with stable over-expression uPAR were constructed successfully.Overexpression of uPAR up-regulated the expression of uPA and uPAR,while DADS down-regulated the expression of uPA and uPAR.uPAR overexpression enhanced cell migration and invasion,whereas DADS inhibi-ted the migration and invasion of uPAR-overexpression cells.DADS inhibited EMT in SW480 cells by down-regulating the expression of Vimentin and matrix metalloprotein(MMP)-9,and up-regulating the expression of E-cadherin and tissue inhibitor of metalloprotein-ase(TIMP)-3.The results of nude mouse experiments showed that DADS can inhibit uPAR overexpression in SW480 cells and EMT in vivo.Conclusion DADS inhibits human colon cancer SW480 cell invasion and EMT by negatively regulating uPAR/uPA sig-naling pathway in vivo and in vitro.
diallyl disulfidehuman colon cancer cellsuPAR/uPA signalinvasionEMTin vivo and in vitro
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