title: Silencing of decoy receptor 3 (DcR3) expression by siRNA in pancreatic carcinoma cells induces Fas ligand-mediated apoptosis in vitro and in vivo.
abstract: Decoy receptor 3 (DcR3) is abundantly expressed in human tumors and protects cells from a wide range of apoptotic stimuli. In this study, we demonstrate that DcR3 is overexpressed in pancreatic carcinoma cells, and that the pancreatic carcinoma cell lines, Panc-1 and SW1990, are resistant to Fas ligand (FasL)-mediated apoptosis. To further define the function of DcR3 in cell growth and apoptosis, we used small interfering RNA (siRNA) to knockdown the expression of the DcR3 gene in Panc-1 and SW1990 cells. Our results revealed that the silencing of DcR3 expression enhanced the inhibitory effects of FasL and reduced the capabiltiy of the cells for proliferation and colony formation in vitro. In addition, the downregulation of DcR3 modulated the cell apoptotic regulators, Fas-associated death domain (FADD), caspase‑3 and caspase‑8, thus triggering cell apoptosis. Furthermore, the knockdown of DcR3 inhibited the growth of Panc-1 tumor xenografts. Taken together, our findings indicate that DcR3 is important in cancer progression and may be a used as a potential therapeutic target for the gene therapy of pancreatic carcinoma.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Shiduo
authors.initials: S
authors.lastname: Song
authors.forename: Songbin
authors.initials: S
authors.lastname: He
authors.forename: Zhenxin
authors.initials: Z
authors.lastname: Wang
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.forename: Dechun
authors.initials: D
authors.lastname: Li
authors.forename: Dongming
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008297:Male; D051379:Mice; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000235:genetics* / Q000378:metabolism; D047368:Tumor Burden / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D053222:Fas Ligand Protein; D034741:RNA, Small Interfering; D053323:Receptors, Tumor Necrosis Factor, Member 6b; C505911:TNFRSF6B protein, human