Prostate Cancer Scientific Abstracts - Y

Welcome to the Prostate Cancer Guide scientific abstracts, author section Y. Here you will find abstracts from the latest research being carried out in the field.

This section is recommended for people who have a scientific interest in prostate cancer. It is recommended that people without prior knowledge of prostate cancer visit the more general areas of this site (Prostate Cancer Guide).

Abstract Authors

 

Latest Prostate Cancer Abstract

Journal: BJU International

Issue: 2006, 97(6):1300-8.

Pubmed ID: 16686729

Authors: Yamanaka K, Rocchi P, Miyake H, Fazli L, So A, Zangemeister-Wittke U, Gleave ME.

Title: Induction of apoptosis and enhancement of chemosensitivity in human prostate cancer LNCaP cells using bispecific antisense oligonucleotide targeting Bcl-2 and Bcl-xL genes.

OBJECTIVE To determine whether a specifically designed bispecific (Bcl-2/Bcl-xL) antisense oligonucleotide induces apoptosis and enhances chemosensitivity in human prostate cancer LNCaP cells, as Bcl-2 and Bcl-xL are both anti-apoptotic genes associated with treatment resistance and tumour progression in many malignancies, including prostate cancer.

MATERIALS AND METHODS Inhibition of Bcl-2 and Bcl-xL expression by the bispecific antisense oligonucleotide was evaluated using real-time reverse transcription-polymerase chain reaction and Western blotting, while growth inhibition and induction of apoptosis were analysed by a crystal violet assay, flow cytometry and Western blotting of apoptosis-relevant proteins. The effect of combined treatment with bispecific antisense oligonucleotide and chemotherapy or small-interference RNA (siRNA) targeting the clusterin gene was also investigated.

RESULTS Bispecific antisense oligonucleotide reduced Bcl-2 and Bcl-xL expression in LNCaP cells in a dose-dependent manner. There was cell growth inhibition, increases in the sub-G0-G1 fraction, and cleavage of caspase-3 and poly(ADP-Ribose) polymerase proteins in LNCaP cells after bispecific ASO treatment. Interestingly, Bcl-2/Bcl-xL bispecific antisense oligonucleotide treatment also resulted in the down-regulation of Mcl-1 and up-regulation of Bax. The sensitivity of LNCaP cells to mitoxantrone, docetaxel or paclitaxel was significantly increased, reducing the 50% inhibitory concentration by 45%, 80% or 90%, respectively. Furthermore, the apoptotic induction by Bcl-2/Bcl-xL bispecific antisense oligonucleotide was synergistically enhanced by siRNA-mediated inhibition of clusterin, a cytoprotective chaperone that interacts with and inhibits activated Bax.

CONCLUSIONS These findings support the concept of the targeted suppression of Bcl-2 anti-apoptotic family members using multitarget inhibition strategies for prostate cancer, through the effective induction of apoptosis.

Contact: The Prostate Centre, Vancouver General Hospital, Vancouver, Canada.