首页|Targeting X-linked inhibitor of apoptosis protein inhibits pancreatic cancer cell growth through p-Akt depletion

Targeting X-linked inhibitor of apoptosis protein inhibits pancreatic cancer cell growth through p-Akt depletion

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AIM:To determine whether lentivirus-mediated shRNA targeting the X-linked inhibitor of apoptosis protein (XIAP) gene could be exploited in the treatment of pancreatic cancer.METHODS:Human pancreatic cancer cells Panc-1,Mia-paca2,Bxpc-3 and SW1990,infected with lentivirus,were analyzed by real-time polymerase chain reaction (PCR).Western blotting was used to examine XIAP protein levels,survivin and p-Akt to confirm the result of real-time PCR and determine the possible mechanism.The 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to measure IC50 to determine chemosensitivity to the chemotherapeutic drugs 5-fluorouracil (5-FU) and gemcitabine.A colony assay,MTT assay and a tumorigenicity experiment were used to study cell proliferation in vitro and in vivo.Caspase-3/7 activity,4',6-diamidino2-phenylindole-staining and flow cytometric measurements were used to study apoptosis in 5W1990 cells.RESULTS:XIAP proteins were found to be differentially expressed among pancreatic cancer cell lines Panc-1,Mia-paca2,Bxpc-3 and SW1990.Data of realtime PCR and Western blotting showed that XIAP was reduced persistently and markedly by lentivirusmediated shRNA.Downregulation of XIAP by transfection with XIAP shRNA resulted in decreased p-Akt expression.XIAP shRNA also inhibited the growth of pancreatic cancer cells in vitro and in vivo,enhanced drug-induced apoptosis and increased chemosensitivity to 5-FU and gemcitabine.Results also suggest that inhibition of XIAP and subsequent p-Akt depletion may have an anti-tumor effect through attenuating the ability of cancer cells to survive.CONCLUSION:Lentivirus-mediated gene therapy is an attractive strategy in the treatment of pancreatic cancer and justifies the use of lentivirus in pancreatic cancer gene therapy studies.

Pancreatic cancerLentivirus-mediated shRNAX-linked inhibitor of apoptosis proteinp-AktGene therapyProliferationApoptosis

Chun Jiang、Xiao-Ping Yi、Hong Shen、Yi-Xiong Li

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Department of Gynaecology and Obstetrics, Xiang Ya Hospital, Central South University, Changsha 410008, Hunan Province, China

Department of Radiology, Xiang Ya Hospital,Central South University, Changsha 410008, Hunan Province,China

Medical Research Center, Xiang Ya Hospital,Central South University, Changsha 410008, Hunan Province,China

Department of General Surgery, Xiang Ya Hospital, Central South University, Changsha 410008, Hunan Province, China

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国家自然科学基金湖南省自然科学基金

30872492088JJ3042

2012

10.3748/wjg.v18.i23.2956

世界胃肠病学杂志(英文版)
太原消化病研治中心

世界胃肠病学杂志(英文版)

SCI
影响因子：1.001
ISSN：1007-9327
年,卷(期)：2012.18(23)
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