Enhancement of docetaxel efficacy by zoledronic acid pretreatment in docetaxel-resistant prostate cancer cells (PC-3/R and DU-145/R).
Bildiriler > Özet Bildiri
Yazarlar: Zeki Surmeli, Emir Bozkurt, Ozge Ozer, Harika Atmaca, Asli Kisim, Selim Uzunoglu, Ruchan Uslu, Burcak Karaca
Journal of Clinical Oncology, , , Uluslararası, Özet Bildiri, Wos, cilt 32, ss e16105-e16105
DOI: 10.1200/jco.2014.32.15_suppl.e16105
Özet
e16105 Background: Docetaxel-based chemotherapy is the only globally approved first-line therapy for hormone refractory prostate cancer. Although docetaxel treatment improves survival, all patients will eventually become refractory to docetaxel treatment. Zoledronic acid (ZA) is the most potent member of nitrogen-containing bisphosphonate family and has anti-tumor activity in some types of cancer, including prostate cancer. In this study, we investigated whether ZA pretreatment enhances the cytotoxic and apoptotic effect of docetaxel in docetaxel resistant (Doc-R) prostate cancer cells. Methods: Doc-R prostate cancer cells were pretreated with the increasing concentrations of ZA for 36 h and with the increasing concentrations of docetaxel for additional 36 h. Cell proliferation was assessed by XTT cell proliferation Kit (Roche). Cell Death Detection Elisa Plus Kit (Roche) and Caspase-Glo 3/7 (Invitrogen) assays were used for investigating apoptosis. Results: The sequential treatment of 20 µM ZA followed by 10 nM docetaxel resulted in significantly enhanced cytotoxicity as compared to single agents alone in both at Doc-R prostate cancer cells. Moreover, docetaxel mediated DNA fragmentation and caspase 3/7 activity was increased by ZA pretreatment. Conclusions: These findings strongly suggest that pretreatment with ZA enhances docetaxel-induced cytotoxicity and apoptosis in Doc-R prostate cancer cells. These preliminary results make ZA a good candidate for overcoming docetaxel resistance in prostate cancer.