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01-10-2008 | Original Article

Docetaxel and bortezomib downregulate Bcl-2 and sensitize PC-3-Bcl-2 expressing prostate cancer cells to irradiation

Authors: Wengang Cao, Kathleen T. Shiverick, Kazunori Namiki, Yoshihisa Sakai, Stacy Porvasnik, Cydney Urbanek, Charles J. Rosser

Published in: World Journal of Urology | Issue 5/2008

Abstract

Background

Currently, docetaxel is used to treat hormone-refractory metastatic prostate cancer. Docetaxel not only inhibits microtubule formation but can also downregulate expression of Bcl-2, a known antiapoptotic oncogene. Furthermore, the 26S proteasome inhibitor bortezomib can downregulate Bcl-2 expression. Previously, we demonstrated that overexpression of Bcl-2 renders cells resistant to radiation therapy. In this study, we investigated whether treating human prostate cancer cells with docetaxel, bortezomib, or both could modulate Bcl-2 expression and whether such modulation could render Bcl-2-overexpressing cells more susceptible to radiation.

Methods

PC-3-Bcl-2 and PC-3-Neo human prostate cancer cells treated with docetaxel and/or bortezomib in addition to irradiation were analyzed in vitro for proliferation, clonogenic survival, cell cycle phase distribution, and expression of Bcl-2 and Bcl-xL proteins.

Results

Docetaxel and bortezomib alone had significant cytotoxic effects. In addition, docetaxel, bortezomib, or radiation resulted in a G2M phase arrest in PC-3-Bcl-2, whereas only docetaxel or radiation did so in PC-3-Neo cells. Both cell lines were more sensitized to radiation’s killing effects when treated with the combination of docetaxel and bortezomib than when treated with either agent alone. Furthermore, docetaxel and bortezomib-treated cells exhibited marked changes in the expression of Bcl-2 and Bcl-xL.

Conclusions

This is the first study to demonstrate that docetaxel and bortezomib in combination can effectively sensitize Bcl-2-overexpressing human prostate cancer cells to radiation effects by modulating the expression of key members of the Bcl-2 family. Together, these findings warrant further evaluation of the combination of docetaxel and bortezomib in prostate cancer.

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Title: Docetaxel and bortezomib downregulate Bcl-2 and sensitize PC-3-Bcl-2 expressing prostate cancer cells to irradiation
Authors: Wengang Cao
Kathleen T. Shiverick
Kazunori Namiki
Yoshihisa Sakai
Stacy Porvasnik
Cydney Urbanek
Charles J. Rosser
Publication date: 01-10-2008
Publisher: Springer-Verlag
Published in: World Journal of Urology / Issue 5/2008
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI: https://doi.org/10.1007/s00345-008-0289-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Docetaxel and bortezomib downregulate Bcl-2 and sensitize PC-3-Bcl-2 expressing prostate cancer cells to irradiation

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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