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...

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Veröffentlicht in:The Prostate 2005-09, Vol.65 (1), p.10-19
Hauptverfasser: Hayashi, Norihiro, Asano, Koji, Suzuki, Hideaki, Yamamoto, Tetsuhisa, Tanigawa, Nobuhiko, Egawa, Shin, Manome, Yoshinobu
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container_end_page 19
container_issue 1
container_start_page 10
container_title The Prostate
container_volume 65
creator Hayashi, Norihiro
Asano, Koji
Suzuki, Hideaki
Yamamoto, Tetsuhisa
Tanigawa, Nobuhiko
Egawa, Shin
Manome, Yoshinobu
description 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. © 2005 Wiley‐Liss, Inc.
doi_str_mv 10.1002/pros.20232
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subjects Adenoviridae - genetics
adenovirus vector
Animals
antisense
Antisense Elements (Genetics) - pharmacology
Apoptosis
Cell Line, Tumor
Cell Proliferation
chemotherapy
Etoposide - pharmacology
Humans
Inhibitor of Apoptosis Proteins
Male
Mice
Mice, Inbred BALB C
Microtubule-Associated Proteins - antagonists & inhibitors
Microtubule-Associated Proteins - genetics
Neoplasm Proteins - antagonists & inhibitors
Neoplasm Proteins - genetics
Neoplasm Transplantation
prostate cancer
Prostatic Neoplasms - drug therapy
Prostatic Neoplasms - pathology
survivin
Taxoids - pharmacology
Transplantation, Heterologous
title Adenoviral infection of survivin antisense sensitizes prostate cancer cells to etoposide in vivo
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