目的： 探讨包含目的蛋白功能结构域的Smac合成肽能否增强胰腺癌细胞的化疗药物敏感性及其作用机制。 方法： 化学合成SmacN7细胞可穿透融合多肽，共沉淀实验观察SmacN7细胞穿透肽与胰腺癌Panc-1细胞内的XIAP的相互作用，应用流式细胞术检测SmacN7细胞穿透肽与顺铂、5-FU联用对Panc-1细胞凋亡的影响，MTT法检测SmacN7细胞穿透肽应用前后Panc-1细胞的化疗药物敏感性。 结果： SmacN7融合多肽能与内源性XIAP结合，明显下调Panc-1细胞XIAP表达水平，显著增强顺铂或5-FU诱导的Panc-1细胞凋亡，使其对顺铂、5-FU的药物半数抑制浓度(IC50)分别降低1.98倍、2.62倍。 结论： 应用包含目的蛋白功能结构域的Smac合成肽能靶向下调胰腺癌Panc-1细胞XIAP表达，显著提高其化疗敏感性，为胰腺癌的生物治疗协同化疗提供了新思路

Objectivev: To investigate whether synthetic Smac peptides containing the seven N-terminal residues essential for XIAP inactivation would increase chemo-sensitivity of pancreatic cancer cells. Methods: SmacN7 penetratin peptide was synthesized and delivered into Panc-1 cells. Interaction between SmacN7 penetratin peptide and XIAP was tested by pull-down assays. The proportions of apoptosis of Panc-1 cells induced by cisplatin or 5-fluorouracil (5-FU) in the presence and absence of SmacN7 peptides were analyzed by flow cytometry. The chemo-sensitivity of Panc-1 cells before and after treated with SmacN7 peptides was evaluated by tetrazolium bromide (MTT) assay. Results: SmacN7 penetratin peptide could successfully interact with endogenous XIAP, greatly down-regulated of XIAP expression and significantly enhanced cisplatin or 5-FU induced apoptosis of Panc-1 cells. Combining treated with SmacN7 penetratin peptide, the 50% inhibitory concentration (IC50) to cisplatin or 5-FU in Panc-1cells was markedly decreased to 1.98 and 2.62 fold respectively. Conclusion: SmacN7 penetratin peptide could act as a cell-permeable IAP inhibitor and sensitize Panc-1 cells to anticancer drug-induced apoptosis. These findings may lead to a novel approach to enhance chemotherapeutic responses in pancreatic cancer.

深圳市科技局资助课题（NO. 200304250)