目的: 探讨RNA干扰沉默诱骗受体3(decoy receptor 3，DcR3)基因对胰腺癌细胞放射敏感性的影响及其相关机制。方法: 构建带有DcR3 siRNA序列的稳定表达质粒，通过脂质体转染至胰腺癌AsPC-1细胞株，设对照组、siRNA(-)阴性对照组和DcR3 siRNA组，应用Western blotting检测AsPC-1细胞中DcR3表达的变化，平板克隆形成实验检测转染DcR3 siRNA后AsPC-1细胞放射敏感性的变化，流式细胞术检测细胞凋亡，RT-PCR和Western blotting检测Caspase-8、Caspase-3和PARP-1表达的变化。结果: DcR3 siRNA 组细胞中DcR3蛋白表达水平较对照或siRNA(-)组明显降低(均P＜0.01)；DcR3 siRNA组的克隆形成率明显低于对照或siRNA(-)组，其存活分数（survival fraction,SF）降低、α/β比值升高（均P＜0.01）；放射后DcR3 siRNA组肿瘤细胞凋亡率明显高于对照或siRNA(-)组（均P＜0.01）；转染DcR3siRNA后可以明显上调Caspase-8、Caspase-3的表达和下调PARP-1的表达。 结论: RNA干扰沉默DcR3基因通过激活凋亡因子Caspase-8和Caspase-3促进细胞凋亡，从而增加胰腺癌细胞对放射的敏感性。

Objective: To investigate the effect of siRNA targeting decoy receptor 3 gene on the radiosensitivity of pancreatic cancer cells and its related mechanism. Methods: Plasmid stably expressing DcR3 siRNA sequence was constructed and transfected into pancreatic cancer AsPC-1 cell line by liposome; control group, siRNA(-) negative control group and DcR3 siRNA group were set up. Then DcR3 expression in AsPC-1 cells was detected by Western blotting. Effect of DcR3 siRNA transfection on radiation sensitivity of AsPC-1 cells was detected by plate clone for-mation assay. Cell apoptosis was analyzed by Flow cytometry; the expressions of Caspase-8, Caspase-3 and PARP-1 were detected by Western blotting and RT-PCR after transfecting with DcR3 siRNA. Results: The expression of DcR3 protein in DcR3 siRNA group was significantly lower than that in control or siRNA(-) group (P<0.01). The colony formation rate of DcR3 siRNA group was significantly lower than that in control group and siRNA(-) group (P<0.01), and the survival fraction(SF) value of DcR3 siRNA group was decreased and the ratio of α/β was in-creased (P<0.01). The cell apoptosis rate of DcR3 siRNA group was significantly higher than that of control group or siRNA(-) group (P<0.01). DcR3 siRNA could significantly up-regulate the expression of Caspase-8 and Caspase-3 and down-egulatetheexpressionofPARP-.Conclusion:siRNAsilencingDcR3genecanincreasetheradiosensitiv-ityofpancreaticcancercellsbyactivatingthe apoptosis factors Caspase-8 and Caspase-3, promoting cell apoptosis.

湖南省自然科学基金资助项目 (No. 14JJ3136)；郴州市科技局科研基金资助项目(No. CZ2013096)