title: Simultaneous silencing of XIAP and survivin causes partial mesenchymal-epithelial transition of human pancreatic cancer cells via the PTEN/PI3K/Akt pathway.
abstract: Pancreatic cancer has one of the highest mortality rates among malignant tumors and is characterized by rapid invasion, early metastasis and chemoresistance. X-linked inhibitor of apoptosis (XIAP) and survivin are two of the most important members of the IAP family. Previous studies have shown that XIAP and survivin were overexpressed in pancreatic cancer and were closely associated with cell proliferation and chemoresistance to gemcitabine. In the present study, stable inhibition of XIAP and survivin in Panc-1 cells was performed using lentivirus-carried short hairpin RNAs. The expression of XIAP, survivin, E-cadherin, Slug, phosphatase and tensin homolog (PTEN) and phosphorylated Akt was then measured. In addition, cell proliferation, apoptosis, invasion and migration were assessed. The results showed that stable inhibition of XIAP and survivin expression in Panc-1 cells significantly reduced cell proliferation, increased apoptosis and partially reversed the epithelial-mesenchymal transition (EMT). Furthermore, the results of the present study demonstrated that the partial reversal of the EMT was accompanied by inhibited cell invasion and migration as well as increased chemosensitivity to gemcitabine in pancreatic cancer cells; this was indicated to be mediated via the PTEN/phosphatidylinositol 3-kinase/Akt signaling pathway. In conclusion, these results suggested that simultaneous inhibition of XIAP and survivin may be a promising strategy for the treatment of pancreatic cancer.
authors.affiliation: Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Yi
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Tong
authors.initials: T
authors.lastname: Han
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Yi-Xiong
authors.initials: YX
authors.lastname: Li
authors.affiliation: Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Xue-Ying
authors.initials: XY
authors.lastname: Long
authors.affiliation: Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Wen-Zheng
authors.initials: WZ
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D051058:Oncogene Protein v-akt / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage; D015398:Signal Transduction / Q000235:genetics; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics*
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D034741:RNA, Small Interfering; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human