title: YM155 Reverses Statin Resistance in Renal Cancer by Reducing Expression of Survivin.
abstract: The purpose of the present study was to clarify whether treatment with YM155, a novel small-molecule inhibitor of survivin, reverses statin resistance in statin-resistant renal cell cancer (RCC).
  
  
  
  We induced simvastatin resistance in a renal clear cell carcinoma cell line (Caki-1-staR). In vitro and in vivo models were used to test the efficacy of YM155 and simvastatin.
  
  
  
  Survivin gene expression was significantly stronger in Caki-1-staR cells than in its parent cells (Caki-1). In Caki-1-staR cells, YM155 significantly reduced expression of survivin gene and cell proliferation in a dose-dependent manner. Treatment with YM155 significantly reversed simvastatin resistance in Caki-1-staR cells. YM155 significantly inhibited the growth of Caki-1-staR tumors in a nude mouse tumor xenograft model. Furthermore, YM155 significantly enhanced the antitumor effects of simvastatin on Caki-1-staR tumors.
  
  
  
  Our results indicate that inhibition of survivin by YM155 overcomes statin resistance in RCC cells.
authors.affiliation: Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nitta
authors.affiliation: Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Japan hkoike@gunma-u.ac.jp.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Koike
authors.affiliation: Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyao
authors.affiliation: Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Miyazawa
authors.affiliation: Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Kato
authors.affiliation: Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Furuya
authors.affiliation: Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Sekine
authors.affiliation: Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009285:Naphthoquinones / Q000494:pharmacology*; D034622:RNA Interference; D019821:Simvastatin / Q000494:pharmacology*; D000077022:Survivin; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007093:Imidazoles; D051034:Inhibitor of Apoptosis Proteins; D009285:Naphthoquinones; D000077022:Survivin; D019821:Simvastatin; C523798:sepantronium
keywords: Kidney neoplasms; combination; drug therapy; inhibitor of apoptosis proteins; statin