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Title: Proteasome inhibitor bortezomib increases radiation sensitivity in androgen independent human prostate cancer cells
Authors: Göktaş, Serdar
Baran, Yusuf
Ural, Ali Uğur
Yazıcı, Sertaç
Aydur, Emin
Başal, Şeref
Avcu, Ferit
Pekel, Aysel
Dirican, Bahar
Beyzadeoğlu, Murat
Keywords: Androgens
Cancer chemotherapy
Cell strain DU145
Messenger RNA
Prostate cancer
Cancer cells
Publisher: Elsevier Ltd.
Source: Göktaş, S., Baran, Y., Ural, A. U., Yazıcı, S., Aydur, E., Başal, Ş., Avcu, F., Pekel, A., Dirican, B., and Beyzadeoğlu, M. (2010). Proteasome inhibitor bortezomib increases radiation sensitivity in androgen independent human prostate cancer cells. Urology, 75(4), 793-798. doi:10.1016/j.urology.2009.07.1215
Abstract: Objectives: To investigate the effects of a strong proteasome inhibitor, bortezomib alone or in combination with radiotherapy on androgen-independent DU145 human prostate cancer cells. Proteasomes play important roles in cell cycle, proliferation, apoptosis, angiogenesis, and cellular resistance to chemotherapy and radiotherapy. Methods: Increasing concentrations of bortezomib alone or in combination with radiation were applied to DU145 cells and IC50 values that inhibited cell growth by 50% were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium-bromide assay. Apoptosis was determined using annexin V staining by flow cytometry. mRNA levels of proapoptotic caspase-3 and antiapoptotic Bcl-2 genes were examined by reverse transcriptase polymerase chain reaction. Results: The IC50 value of bortezomib was found to be 28 μm although 400- and 800-cGy radiation decreased the cell proliferation by 14% and 28%, respectively. In 400- and 800-cGy radiation applied DU145 cells, IC50 value of bortezomib decreased to 23- and 12 μm, respectively. Exposure to 5 μm bortezomib for 48 hours caused apoptosis in 35% of the population whereas 800-cGy radiation resulted apoptosis in 14% of cells. However, 42% of DU145 cells that were exposed to 800 cGy and 5 μm bortezomib underwent apoptosis. Reverse transcriptase polymerase chain reaction results showed a significant decrease in mRNA levels of antiapoptotic Bcl-2 gene and an increase in proapoptotic caspase-3 gene expression in the combination group compared to control group. Conclusions: Bortezomib increases radiation sensitivity in androgen-independent human DU145 prostate cancer cells through inhibition of Bcl-2 and induction of caspase-3 genes. © 2010 Elsevier Inc. All rights reserved.
ISSN: 0090-4295
Appears in Collections:Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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