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Synthetic N-Terminus of Smac Peptide Sensitize Pancreatic Cancer Cells to Anticancer Drug-Induced Apoptosis by Selective Down-Regulation of XIAP
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Abstract:
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.
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