Proteasome Inhibitor Bortezomib Increases Radiation Sensitivity in Androgen Independent Human Prostate Cancer Cells
Urology, cilt.75, sa.4, ss.793-798, 2010 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 75 Sayı: 4
- Basım Tarihi: 2010
- Doi Numarası: 10.1016/j.urology.2009.07.1215
- Dergi Adı: Urology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.793-798
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
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.