Regulation of growth factors in hormone- and drug-resistant prostate cancer cells by synergistic combination of docetaxel and octreotide.
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.
Erten
Cigdem
C
Division of Medical Oncology, Tulay Aktas Oncology Hospital, Turkey.
Karaca
Burcak
B
Kucukzeybek
Yuksel
Y
Gorumlu
Gurbuz
G
Cengiz
Ercument
E
Gul
Mustafa K
MK
Atmaca
Harika
H
Uzunoglu
Selim
S
Karabulut
Bulent
B
Sanli
Ulus A
UA
Uslu
Ruchan
R
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
D036341:Intercellular Signaling Peptides and Proteins; D043823:Taxoids; D000077143:Docetaxel; D015282:Octreotide