title: The survivin suppressant YM155 potentiates chemosensitivity to gemcitabine in the human pancreatic cancer cell line MiaPaCa-2.
abstract: BACKGROUND
  Survivin is a negative regulator of apoptosis. We evaluated the efficacy of YM155, a selective suppressant of survivin, in combination with gemcitabine in the pancreatic cancer cell line MiaPaCa-2.
  
  
  METHODS
  Expression of survivin was demonstrated by immunoblotting. Cell cycle progression was determined by flow cytometric analysis. Cell viability was assayed using the trypan blue exclusion assay.
  
  
  RESULTS
  Gemcitabine up-regulated survivin expression, whereas treatment with YM155 suppressed the expression of survivin. Concomitant treatment with YM155 enhanced chemosensitivity to gemcitabine, which was accompanied by a decrease in the expression of survivin. Knockdown of endogenous survivin via RNA interference also enhanced the sensitivity to gemcitabine. In addition, YM155 potentiated the antitumor effect of gemcitabine in xenograft tumors of MiaPaCa-2.
  
  
  CONCLUSIONS
  YM155 potentiates chemosensitivity to gemcitabine in pancreatic cancer cells by suppressing the induction of survivin. Combination treatment with gemcitabine and YM155 may be a potential therapeutic strategy for the treatment of pancreatic cancer that warrants further clinical investigation.
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Dok Hyun
authors.initials: DH
authors.lastname: Yoon
authors.forename: Jae-Sik
authors.initials: JS
authors.lastname: Shin
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Jin
authors.forename: Seung-Woo
authors.initials: SW
authors.lastname: Hong
authors.forename: Kyung A
authors.initials: KA
authors.lastname: Jung
authors.forename: Seung-Mi
authors.initials: SM
authors.lastname: Kim
authors.forename: Yong Sang
authors.initials: YS
authors.lastname: Hong
authors.forename: Kyu-Pyo
authors.initials: KP
authors.lastname: Kim
authors.forename: Jae-Lyun
authors.initials: JL
authors.lastname: Lee
authors.forename: Cheolwon
authors.initials: C
authors.lastname: Suh
authors.forename: Jung Shin
authors.initials: JS
authors.lastname: Lee
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors*; D051379:Mice; D008807:Mice, Inbred BALB C; D009285:Naphthoquinones / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D000077022:Survivin; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D007093:Imidazoles; D051034:Inhibitor of Apoptosis Proteins; D009285:Naphthoquinones; D034741:RNA, Small Interfering; D000077022:Survivin; D003841:Deoxycytidine; C523798:sepantronium; D000093542:Gemcitabine