BACKGROUND:TNF-related apoptosis-inducing ligand (TRAIL) is a death ligand of the TNF-superfamily that has been implicated in inducing apoptosis in some tumor cells. The purpose of this study was to ifnd out if TRAIL could induce the expression of uPA, IL-8, MMP-7 and MMP-9. and to explore the corresponding potential signaling transduction pathway in pancreatic cancer cells. METHODS:Colo357wt, Panc89 and PancTuⅠ cell lines were stimulated by TRAIL (100 ng/ml). Crystal violet cell vitality assay was used to check the sensitivity to TRAIL-induced apoptosis. Real-time RT-PCR tested the expression of uPA, IL-8, MMP-7 and MMP-9. RESULTS:TRAIL can stimulate the expression of uPA, IL-8, MMP-7 and MMP-9 in pancreatic cancer cell lines, especially in Colo357wt. The members of caspases, MEK1/2, PKC, and NF-κB are involved in TRAIL-induced expression of uPA, IL-8, MMP-7 and MMP-9. Furthermore, caspases play a different role in Colo357wt, Panc89 and PancTuⅠ. CONCLUSIONS:TRAIL-treatment may result in the enhancement of invasion involving the signaling pathwaysof caspases, MEK1/2, PKC and NF-κB, in pancreatic cancer cells. It points to the necessity to carefully evaluate in vivo side effects of TRAIL.