XIAP is related to the chemoresistance and inhibited its expression by RNA interference sensitize pancreatic carcinoma cells to chemotherapeutics.
OBJECTIVE
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.
Li
Yixiong
Y
Department of General Surgery, Xiangya Hospital, Hunan, China. jzyuan@tom.com
Jian
Zhiyuan
Z
Xia
Kun
K
Li
Xiaogang
X
Lv
Xinsheng
X
Pei
Haiping
H
Chen
Zhikang
Z
Li
Jindong
J
D017209:Apoptosis; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D034622:RNA Interference; D012333:RNA, Messenger / Q000032:analysis; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000093542:Gemcitabine
D012333:RNA, Messenger; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D003841:Deoxycytidine; D005472:Fluorouracil; D000093542:Gemcitabine