title: [X-linked inhibitor of apoptosis protein (XIAP) and Survivin suppression on human pancreatic cancer cells Panc-1 proliferation and chemosensitivety].
abstract: OBJECTIVE
  To investigate the effect on cell proliferation and chemosensitivity of human pancreatic cancer cells Panc-1 after X-linked inhibitor of apoptosis protein (XIAP) and Survivin are inhibited simultaneously, and to compare it with the separate gene suppression strategy by which expression of XIAP or Survivin is inhibited respectively.
  
  
  METHODS
  Panc-1 (Panc-1-X, Panc-1-S and Panc-1-XS) in which expression of XIAP and/or Survivin was inhibited, was established by using XIAP-shRNA lentiviral and Survivin-shRNA lentiviral we had built. The expressions of XIAP and Survivin mRNA and protein were evaluated by Real-time PCR and Semi-quantitatively Western blot analysis; cell proliferation was investigated by cell counting and colony formation assay; cell apoptosis was investigated by Caspase-3/7 activity assay kit and flow cytometry; gemcitabine (Gem) chemosensitivity was investigated by MTT assay.
  
  
  RESULTS
  The pancreatic cell line Panc-1 in which the expression of XIAP and/or Survivin was stablely inhibited was successfully established. The cell proliferation of Panc-1-XS cells decreased significantly. The colony formation rate of Panc-1-XS cells (10.12%± 1.33%), was significantly lower than that of Panc-1-XncSnc cells (96.61% ± 7.89%) and Panc-1 cells (100.28% ± 8.97%) respectively (P<0.05). After being treated by 0.5 mg/L Gem for 24 h, the Caspase-3/7 relative activity of Panc-1-XS cells (15.02 ± 0.57) was significantly higher than that of Panc-1 cells and Panc-1-XncSnc cells (8.87 ± 0.19 and 9.05 ± 0.23, respectively; P<0.05); and the rate of apoptosis of Panc-1-XS cells (24.09% ± 2.75%) was significantly higher than that of Panc-1-XncSnc cells and Panc-1 cells (12.09% ± 1.97% and 12.06% ± 1.22%, respectively; P<0.05). The IC50 value of Panc-1-XS cells [(0.47 ± 0.04) mg/L] was significantly lower than that of Panc-1-XncSnc cells [(2.18 ± 0.13) mg/L] and Panc-1 cells [(2.13 ± 0.18) mg/L, P<0.05]. Further testing also showed that, the IC50 value of Panc-1-XS cells [(0.47 ± 0.04) mg/L] was significantly lower than that of Panc-1-X cells [(0.76 ± 0.07) mg/L] and Panc-1-S cells [(0.87 ± 0.09) mg/L, P<0.05].
  
  
  CONCLUSIONS
  The cell proliferation of Panc-1 cells was significantly suppressed and the Gem chemosensitivity was significantly enhanced after expressions of XIAP and Survivin were inhibited simultaneously, and significantly better than the strategy in which expressions of XIAP and Survivin were inhibited separately.
authors.affiliation: Department of Gerneral Surgery, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Hong-yan
authors.initials: HY
authors.lastname: Zai
authors.forename: Xiao-ping
authors.initials: XP
authors.lastname: Yi
authors.forename: Yi-xiong
authors.initials: YX
authors.lastname: Li
authors.forename: Xue-ying
authors.initials: XY
authors.lastname: You
authors.forename: Li-ping
authors.initials: LP
authors.lastname: Cao
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000077022:Survivin; D014407:Tumor Cells, Cultured; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human