Regulation of growth factors in hormone- and drug-resistant prostate cancer cells by synergistic combination of docetaxel and octreotide
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Date
2009
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Abstract
OBJECTIVE To evaluate the effects of combined treatment with docetaxel and octreotide, a somatostatin analogue, on human hormone- and drug-refractory prostate cancer cell lines, PC-3 and DU-145, and on some growth factors related to tumour growth and angiogenesis in prostate cancer. MATERIALS AND METHODS A cell proliferation assay was used to assess the cytotoxicity of the drugs. To verify apoptosis, both DNA fragmentation (by enzyme-linked immunosorbent assay) and caspase 3/7 activity were measured. We also investigated the effect of combined docetaxel and octreotide on growth factors secreted from prostate cancer cells using a human growth factor antibody array. RESULTS The combination of docetaxel and octreotide resulted in significant synergistic cytotoxic activity and apoptosis, which was dose- and time-dependent. The combined treatment also resulted in significantly less secretion of stem cell factor and platelet-derived growth factor-AB in PC-3 cells, and transforming growth factor-β and basic fibroblast growth factor in DU-145 cells, than in untreated controls. CONCLUSION Octreotide, a somatostatin analogue, combined with docetaxel might provide a rationale treatment option for hormone-refractory prostate cancer cells, not only by direct inhibition of cell proliferation but also by inhibiting the secretion of growth factors. © 2009 BJU International.
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Antineoplastic Combined Chemotherapy Protocols , Cell Line, Tumor , Drug Resistance, Neoplasm , Drug Synergism , Enzyme-Linked Immunosorbent Assay , Humans , Intercellular Signaling Peptides and Proteins , Male , Neoplasms, Hormone-Dependent , Octreotide , Prostate , Prostatic Neoplasms , Taxoids , Treatment Outcome , basic fibroblast growth factor , caspase 3 , caspase 7 , docetaxel , octreotide , platelet derived growth factor AB , stem cell factor , transforming growth factor beta , angiogenesis , apoptosis , article , cancer cell culture , cell proliferation , clinical evaluation , concentration response , controlled study , DNA fragmentation , drug cytotoxicity , drug effect , drug potentiation , enzyme activity , enzyme linked immunosorbent assay , human , human cell , male , priority journal , prostate cancer , protein secretion , regulatory mechanism , tumor growth