title: Regulation of growth factors in hormone- and drug-resistant prostate cancer cells by synergistic combination of docetaxel and octreotide.
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-beta 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.
authors.affiliation: Division of Medical Oncology, Tulay Aktas Oncology Hospital, Turkey.
authors.forename: Cigdem
authors.initials: C
authors.lastname: Erten
authors.forename: Burcak
authors.initials: B
authors.lastname: Karaca
authors.forename: Yuksel
authors.initials: Y
authors.lastname: Kucukzeybek
authors.forename: Gurbuz
authors.initials: G
authors.lastname: Gorumlu
authors.forename: Ercument
authors.initials: E
authors.lastname: Cengiz
authors.forename: Mustafa K
authors.initials: MK
authors.lastname: Gul
authors.forename: Harika
authors.initials: H
authors.lastname: Atmaca
authors.forename: Selim
authors.initials: S
authors.lastname: Uzunoglu
authors.forename: Bulent
authors.initials: B
authors.lastname: Karabulut
authors.forename: Ulus A
authors.initials: UA
authors.lastname: Sanli
authors.forename: Ruchan
authors.initials: R
authors.lastname: Uslu
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015282:Octreotide / Q000008:administration & dosage; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D043823:Taxoids; D000077143:Docetaxel; D015282:Octreotide