title: Adenoviral infection of survivin antisense sensitizes prostate cancer cells to etoposide in vivo.
abstract: BACKGROUND
  We aimed to investigate whether use of a survivin antisense fragment carried by an adenovirus vector (Ad.survivin-AS) could enhance the therapeutic efficacy of chemotherapy for androgen-independent prostate cancer.
  
  
  METHODS
  We used Ad.survivin-AS to promote apoptosis through inhibition of survivin expression. Recombinant adenoviruses alone or in combination with chemotherapeutic agents were tested for anti-cancer activity both in vitro and in vivo.
  
  
  RESULTS
  Infection with Ad.survivin-AS strongly inhibited survivin expression in a dose- and time-dependent manner, resulting in significant antitumor activity in vitro and in vivo. Downregulation of survivin expression potentiated induction of apoptosis by the chemotherapeutic agents docetaxel and etoposide in DU145 cells. In particular, the combination of etoposide and Ad.survivin-AS demonstrated dramatic growth inhibition with no tumor regrowth being observed during the experimental period.
  
  
  CONCLUSIONS
  The prominent synergy of this combination may provide a basis for clinical application of Ad.survivin-AS as a chemosensitizer of etoposide.
authors.affiliation: Department of Urology, Jikei University School of Medicine, Nishi-shinbashi, Tokyo, Japan. norihiro@jikei.ac.jp
authors.forename: Norihiro
authors.initials: N
authors.lastname: Hayashi
authors.forename: Koji
authors.initials: K
authors.lastname: Asano
authors.forename: Hideaki
authors.initials: H
authors.lastname: Suzuki
authors.forename: Tetsuhisa
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Tanigawa
authors.forename: Shin
authors.initials: S
authors.lastname: Egawa
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Manome
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D016375:Antisense Elements (Genetics) / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000077143:Docetaxel; D005047:Etoposide / Q000494:pharmacology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077022:Survivin; D043823:Taxoids / Q000494:pharmacology; D014183:Transplantation, Heterologous
chemical_list: D016375:Antisense Elements (Genetics); C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D043823:Taxoids; D000077143:Docetaxel; D005047:Etoposide