title: Octreotide in combination with AT-101 induces cytotoxicity and apoptosis through up-regulation of somatostatin receptors 2 and 5 in DU-145 prostate cancer cells.
abstract: Prostate cancer (PCa) is the most common type of cancer among males. Although survival rate of early-stage PCa is high, treatment options are very limited for recurrent disease. In this study, the possible synergistic cytotoxic and apoptotic effect of octreotide in combination with AT-101 was investigated in DU-145 hormone and drug refractory prostate cancer cell line. To enlighten the action mechanisms of the combination treatment, expression levels of somatostatin receptors 2 and 5 (SSTR2 and SSTR5) were also investigated. Cell viability was measured by XTT assay. Apoptosis was assessed through DNA fragmentation analysis and caspase 3/7 assay. mRNA and protein levels of SSTR2 and SSTR5 were evaluated by qRT-PCR and western blot analysis, respectively. Octreotide in combination with AT-101 inhibited cell viability and induced apoptosis synergistically in DU-145 cells as compared to any agent alone. Combination treatment increased both SSTR2 and SSTR5 mRNA and protein levels in DU-145 cells. The data suggest that this combination therapy may be a good candidate for patients with advanced metastatic PCa do not respond to androgen deprivation.
authors.affiliation: Department of Internal Medicine, School of Medicine, Tepecik Research and Education Hospital, Izmir, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Degirmenci
authors.affiliation: Department of Medical Oncology, School of Medicine, Ege University, Izmir, Turkey.
authors.forename: Atike Pinar
authors.initials: AP
authors.lastname: Erdogan
authors.affiliation: Department of Medical Oncology, School of Medicine, Ege University, Izmir, Turkey.
authors.forename: Gulcan
authors.initials: G
authors.lastname: Bulut
authors.affiliation: Department of Biology, Faculty of Science and Letters, Celal Bayar University, Manisa, Turkey.
authors.forename: Harika
authors.initials: H
authors.lastname: Atmaca
authors.affiliation: Department of Medical Biology, School of Medicine, Celal Bayar University, Manisa, Turkey.
authors.forename: Selim
authors.initials: S
authors.lastname: Uzunoglu
authors.affiliation: Department of Medical Oncology, School of Medicine, Ege University, Izmir, Turkey.
authors.forename: Burcak
authors.initials: B
authors.lastname: Karaca
authors.affiliation: Department of Medical Oncology, School of Medicine, Ege University, Izmir, Turkey.
authors.forename: Bulent
authors.initials: B
authors.lastname: Karabulut
authors.affiliation: Department of Medical Oncology, School of Medicine, Ege University, Izmir, Turkey. ruchan.uslu@ege.edu.tr.|Tulay Aktas Oncology Hospital, Ege University School of Medicine, 35100, Bornova, Izmir, Turkey. ruchan.uslu@ege.edu.tr.
authors.forename: Ruchan
authors.initials: R
authors.lastname: Uslu
mesh_terms: D000728:Androgens / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006072:Gossypol / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D015282:Octreotide / Q000008:administration & dosage; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017481:Receptors, Somatostatin / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000728:Androgens; D017481:Receptors, Somatostatin; C094573:somatostatin receptor 5; C093733:somatostatin receptor 2; D006072:Gossypol; D015282:Octreotide; C028178:gossypol acetic acid
keywords: AT-101; Apoptosis; Cell viability; Octreotide; SSTR2 and SSTR5