XIAP is related to the chemoresistance and inhibited its expression by RNA interference sensitize pancreatic carcinoma cells to chemotherapeutics.

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Li Y, Jian Z, Xia K, Li X, Lv X, Pei H, Chen Z, Li J

XIAP is related to the chemoresistance and inhibited its expression by RNA interference sensitize pancreatic carcinoma cells to chemotherapeutics.

Pancreas. 2006 Apr;32(3):288-96.

PubMed ID

16628085 [ View in PubMed

]

Abstract

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 mug/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.