Abstract: Background and purpose: It has been demonstrated that decoy receptor 3 (DcR3) is overexpressed in pancreatic cancer, and DcR3 correlates with the expression of FasL, which may contribute to chemotherapy resistance in pancreatic cancer. The purpose of this study was to investigate the effect of RNA interference silencing DcR3 gene on chemosensitivity of human pancreatic cancer cells and its possible mechanism. Methods: A stable expression plasmid with DcR3-siRNA sequence was constructed and transfected into human pancreatic cancer cell line AsPC-1 by Lipofectamine^TM2000. The DcR3-expressing pancreatic cancer cells with stable and low expression were selected. The protein expression of DcR3 in AsPC-1 cells was detected by ELISA and Western blot. MTT assay was used to detect the sensitivity of each group of AsPC-1 cells to gemcitabine. Flow cytometry was used to detect the apoptosis of AsPC-1 cells after treatment with gemcitabine. The expressions of FasL, Caspase-8, Caspase-3 and mRNA in AsPC-1 cells were detected by Western blot and real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR). Results: The expression of DcR3 protein in AsPC-1 cells was significantly lower than those in the other control groups. The sensitivity of AsPC-1 cells to gemcitabine was significantly increased after transfection with DcR3- siRNA compared with control and mock cell lines. Transfection of DcR3-siRNA significantly increased the apoptosis of AsPC-1 cells induced by chemotherapeutic drugs. The expression of FasL, Caspase-8 and Caspase-3 protein and mRNA were up-regulated after transfection with DcR3-siRNA. Conclusion: RNA interference silencing DcR3 gene can activate FasL/Caspase apoptosis pathway, promote tumor cell apoptosis and increase the sensitivity of human pancreatic cancer AsPC-1 cells to gemcitabine.

Key words: Decoy receptor 3, RNA interference, Pancreatic cancer, Apoptosis, Chemosensitivity