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XIAP Is Related to the Chemoresistance and Inhibited Its Expression by RNA Interference Sensitize Pancreatic Carcinoma Cells to Chemotherapeutics

Objectives: To explore the exact role does the x-linked inhibitor of apoptosis (XIAP) play in chemoresistance of pancreatic carcinoma cell and the cell sensitivity to chemotherapeutic drugs changed after XIAP is inhibited by RNA interference (RNAi). Methods: Pancreatic carcinoma cell line SW1990 was exposed to 5-fluorouracil (5-fu) with the concentrations of 1.0 and 10 &mgr;g/mL to increase the expression of XIAP. Then 4 RNAi plasmid vectors against XIAP were designed and constructed, then transfected into SW1990. Repressive effect was evaluated by reverse transcriptase polymerase chain reaction and Western blot; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry were performed to determine cell sensitivity to 5-fu and gemcitabine; furthermore, apoptosis is confirmed by Hoechst 33258 stain. Results: XIAP of SW1990 can be up-regulated with the chemoresistance increasing 1.5- and 4-fold after 10 and 30 days induced by 5-fu. Two of the 4 vectors can inhibit the expression of XIAP protein more than 60%. The cells apoptosis index induced by 5-fu and gemcitabine increased greatly after XIAP is inhibited by the RNAi plasmid vectors. Conclusions: XIAP is one of the most important factors in the pancreatic carcinoma chemoresistance, and inhibition of XIAP in pancreatic carcinoma can enhance the cancer sensitivity to chemotherapeutic drugs.