Use of docetaxel in combination with octreotide as a synergistic combination for prostate cancer with apoptotic and antiangiogenic effects.
Bildiriler > Özet Bildiri
Yazarlar: Burcak Karaca, Harika Atmaca, Emir Bozkurt, Canfeza Sezgin, Bulent Karabulut, Ruchan Uslu
Journal of Clinical Oncology, , , Uluslararası, Özet Bildiri, Wos, cilt 32, ss e13515-e13515
DOI: 10.1200/jco.2014.32.15_suppl.e13515
Özet
e13515 Background: In this study, we investigated the possible cytotoxic and apoptotic effects of docetaxel, a standard treatment for hormone refractory prostate cancer, in combination with octreotide in prostate cancer cell lines. Pivotal proteins of angiogenesis were also studied with this combination. Methods: Human prostate cancer cells (DU-145, PC-3 and LNCaP) were treated with the increasing concentrations of drugs alone or in combination for 72h. XTT assay was done to assess cytotoxicity. Apoptosis was shown by DNA fragmentation and Caspase 3/7 activity assays. Changes in apoptosis-related protein expressions were investigated by apoptosis antibody array. The protein levels of pivotal angiogenic molecules, PDGF, FGF,VEGF were detected by Western blot analysis. Results: 10 nM docetaxel+10 nM octreotide combination treatment resulted in synergistic cytotoxicity in a dose-dependent manner in all prostate cancer cells (p<0.05). DNA fragmentation and caspase 3/7 activity were also induced in a dose-dependent manner (p<0.05). Changes in apoptosis related proteins in prostate cancer cells exposed to combination were shown in the Table (p<0.05). There were also significant decreases in protein levels of angiogenic PDGF, FGF, VEGF proteins in combination treated prostate cancer cells. Conclusions: Based on these findings, docetaxel/octreotide combination with synergistic cytotoxic, apoptotic and anti-angiogenic effects might demonstrate a promising combination treatment for prostate cancer in future. Fold change Protein Octreotide Docetaxel Combination (a) Bax 1.8 1.6 3.2 Bad 1.25 1.6 1.93 Fas 3.2 4.6 10.8 Cleaved-Caspase-3 2.3 4.2 8.8 FADD 2.6 2.4 4.7 Phospho p53 1.7 2.3 5.6 Cytochrome c 2.1 3.3 4.8 Smac/DIABLO 3.4 4.7 7.6 XIAP -2.2 -3.6 -4.1 (b) Cleaved-Caspase-3 2 2.1 4.3 Bax 2.6 1.2 2.9 Bcl-2 -2.5 -2.2 -4.6 Bcl-xL -3.2 -2.6 -4.2 P53 2.2 1.8 2.7 Rad17 1.3 1.6 2.2 SMAC/Diablo 2.6 1.4 3.2 cIAP-2 -1.7 -1.1 -2.3 Cytochrome c 2.6 1.8 3.4 HTRA2/Omi 1.4 1.6 2.8 Phospho-p53 2.4 2.3 3.6 (c) Bax 2.2 1.8 4.4 Bad 3 2.1 5.2 Fas 2 1.6 3.2 FADD 2.3 1.9 3.6 TRAIL-R2 2.4 1.8 3.9 Bcl-2 -2.1 -3.4 -5.6 Bcl-xL 1.7 2.2 -3.7 HSP27 -1.2 -2.3 -4.1 Cleaved-Caspase-3 3.4 2.1 7.4 Phospho p53 2.4 3.4 5.5 TNF R1 1.7 2.3 4.6