PMID- 15754318
OWN - NLM
STAT- MEDLINE
DCOM- 20050830
LR  - 20181201
IS  - 0270-4137 (Print)
IS  - 0270-4137 (Linking)
VI  - 64
IP  - 3
DP  - 2005 Aug 1
TI  - Adenovirus-mediated inhibition of survivin expression sensitizes human prostate 
      cancer cells to paclitaxel in vitro and in vivo.
PG  - 293-302
AB  - BACKGROUND: Improvements in the response rates to chemotherapy would represent an 
      important advancement in the care of patients with metastatic prostate cancer. 
      There is accumulating evidence that Survivin, a member of the inhibitor of 
      apoptosis (IAP) family, is associated with both cancer progression and drug 
      resistance. The purpose of this study is to investigate the role of Survivin in 
      paclitaxel-resistance and whether the targeting of Survivin sensitizes prostate 
      cancer cells to paclitaxel. METHODS: Human prostate cell lines PC-3, DU-145, and 
      LNCaP were infected with replication-deficient adenoviruses encoding either 
      wild-type Survivin [pAd-S(WT)], to examine Survivin overexpression effects, or a 
      phosphorylation-defective Survivin Thr34 --> Ala dominant negative mutant 
      [pAd-S(T34A)], to examine Survivin inactivation effects. The effects of wild-type 
      or mutant Survivin on spontaneous and paclitaxel-induced apoptosis were 
      investigated both in vitro and in vivo. RESULTS: Forced overexpression of 
      wild-type Survivin with pAd-S(WT) increased resistance to paclitaxel in all cell 
      lines, both in vitro and in vivo. Inhibition of Survivin using pAd-S(T34A) 
      resulted in a significant increase in the rate of spontaneous and 
      paclitaxel-induced apoptosis in all cell lines, both in vitro and in vivo. This 
      effect was abolished by co-treatment with VAD-CHO (Calbiochem, San Diego, CA), a 
      pan-caspase inhibitor, indicating that Survivin normally mediates resistance to 
      paclitaxel through suppression of caspase-mediated apoptosis. CONCLUSIONS: 
      Survivin mediates paclitaxel-resistance in prostate cancer cells. The inhibition 
      of Survivin sensitizes prostate cancer cells to paclitaxel-induced apoptosis 
      through a caspase-dependant mechanism in vitro and in vivo.
CI  - (c) 2005 Wiley-Liss, Inc.
FAU - Zhang, Min
AU  - Zhang M
AD  - Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical 
      School Boston, Massachusetts 02114, USA.
FAU - Mukherjee, Neelanjan
AU  - Mukherjee N
FAU - Bermudez, R Scott
AU  - Bermudez RS
FAU - Latham, Douglas E
AU  - Latham DE
FAU - Delaney, Meaghan A
AU  - Delaney MA
FAU - Zietman, Anthony L
AU  - Zietman AL
FAU - Shipley, William U
AU  - Shipley WU
FAU - Chakravarti, Arnab
AU  - Chakravarti A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Prostate
JT  - The Prostate
JID - 8101368
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (BIRC5 protein, human)
RN  - 0 (Inhibitor of Apoptosis Proteins)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Survivin)
RN  - EC 3.4.22.- (Caspases)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Adenoviridae/*genetics
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/*pharmacology
MH  - Apoptosis/drug effects
MH  - Caspases/metabolism
MH  - Cell Line, Tumor
MH  - Drug Resistance, Neoplasm/genetics
MH  - Genetic Therapy/methods
MH  - Humans
MH  - In Vitro Techniques
MH  - Inhibitor of Apoptosis Proteins
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - Microtubule-Associated Proteins/*genetics
MH  - Neoplasm Proteins
MH  - Paclitaxel/*pharmacology
MH  - Prostatic Neoplasms/*drug therapy/genetics/pathology
MH  - Survivin
MH  - Up-Regulation/drug effects
EDAT- 2005/03/09 09:00
MHDA- 2005/09/01 09:00
CRDT- 2005/03/09 09:00
PHST- 2005/03/09 09:00 [pubmed]
PHST- 2005/09/01 09:00 [medline]
PHST- 2005/03/09 09:00 [entrez]
AID - 10.1002/pros.20263 [doi]
PST - ppublish
SO  - Prostate. 2005 Aug 1;64(3):293-302. doi: 10.1002/pros.20263.