Adenoviral infection of survivin antisense sensitizes prostate cancer cells to etoposide in vivo.
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.
Hayashi
Norihiro
N
Department of Urology, Jikei University School of Medicine, Nishi-shinbashi, Tokyo, Japan. norihiro@jikei.ac.jp
Asano
Koji
K
Suzuki
Hideaki
H
Yamamoto
Tetsuhisa
T
Tanigawa
Nobuhiko
N
Egawa
Shin
S
Manome
Yoshinobu
Y
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
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