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Docetaxel and bortezomib downregulate Bcl-2 and sensitize PC-3-Bcl-2 expressing prostate cancer cells to irradiation
- Source :
- World journal of urology. 26(5)
- Publication Year :
- 2008
-
Abstract
- 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.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.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.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.
- Subjects :
- Male
Radiation-Sensitizing Agents
Urology
medicine.medical_treatment
Down-Regulation
Antineoplastic Agents
Docetaxel
Bortezomib
Prostate cancer
medicine
Tumor Cells, Cultured
Humans
neoplasms
Oncogene
business.industry
Cancer
Prostatic Neoplasms
medicine.disease
Boronic Acids
Radiation therapy
Proto-Oncogene Proteins c-bcl-2
Pyrazines
Immunology
Cancer cell
Cancer research
Proteasome inhibitor
Taxoids
business
medicine.drug
Subjects
Details
- ISSN :
- 07244983
- Volume :
- 26
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- World journal of urology
- Accession number :
- edsair.doi.dedup.....4c7cf8ec7811bcc89b3c088d153da9a9