中德临床肿瘤学杂志(英文版)2006，Vol.5Issue(1)：31-35,5.
凋亡抑制蛋白XIAP和促凋亡因子Smac在胰腺癌化疗抵抗中的调控作用
Regulatory Effects of X-linked Inhibitor of Apoptosis Protein and Pro-apoptotic Protein Smac on Apoptosis Resistance to Chemotherapy in Pancreatic Cancer Cells
摘要
Abstract
Objective: To investigate the relation of X-linked inhibitor of apoptosis (XIAP) and secondmitochondria-derived activator of caspase (Smac) signaling pathway to chemoresistance in human pancreatic cancer Panc-1 and BXPC-3 cells. Methods: Apoptosis and the changes of XIAP expression in permeabilized cells induced by cisplatin and 5-fluorouracil (FU) were measured by flow cytometry. The cytosolic expression of XIAP, Smac and caspase-3 was detected by Western blot. A recombinant plasmid vector pEGFP-N1/Smac was constructed and transfected into of Panc-1 cells. The effect of cytosolic over expression of Smac on apoptosis of Panc-1 cells was evaluated by flow cytometry. Results: Pane-1 was more resistant to cisplatin or 5-FU induced apoptosis than BXPC-3. Western blot revealed that chemore sistant Pane-1 highly expressed XIAP, and increased cytosolic expression of Smac might be responsible for the marked down-regulation of XIAP in chemo-sensitive BXPC-3 cells after exposure to cisplatin or 5-FU. Furthermore, cytosolic overexpression of Smac could significantly down-regulate the levels of XIAP and promote the activity of caspase-3, as well as sensitize Panc-1 cells to anticancer drug-induced apopto sis. Conclusion: Anticancer drug-induced apoptosis requires mitochondrial release of Smac and downregulation of XIAP, which may be an important determinant of chemo-sensitivity in pancreatic cancer cells. Up-regulation of cytosolic expression of Smac may act as an effective modifying signal to overcome apoptosis resistance to chemotherapy in pancreatic cancer cells.关键词
X-linked inhibitor of apoptosis protein/second mitochondria-derived activator of caspase/pancreatic cancer/apoptosis/chemoresistanceKey words
X-linked inhibitor of apoptosis protein/second mitochondria-derived activator of caspase/pancreatic cancer/apoptosis/chemoresistance分类
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杜冀晖,张厚德,雷萍,苏卓娃,郑芳,龚非力..凋亡抑制蛋白XIAP和促凋亡因子Smac在胰腺癌化疗抵抗中的调控作用[J].中德临床肿瘤学杂志(英文版),2006,5(1):31-35,5.基金项目
This work was supported by grants from Foundation of Science and Technology of Shenzhen (No. 200304250). （No. 200304250）
