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
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Date
2016
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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. © 2015, International Society of Oncology and BioMarkers (ISOBM).
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Androgens , Apoptosis , Cell Line, Tumor , Cell Proliferation , Cell Survival , Drug Resistance, Neoplasm , Drug Synergism , Gene Expression Regulation, Neoplastic , Gossypol , Humans , Male , Octreotide , Prostatic Neoplasms , Receptors, Somatostatin , caspase 3 , caspase 7 , isosorbide , messenger RNA , octreotide , somatostatin receptor 2 , somatostatin receptor 5 , androgen , gossypol , gossypol acetic acid , octreotide , somatostatin receptor , somatostatin receptor 2 , somatostatin receptor 5 , antineoplastic activity , Article , cell viability , controlled study , DNA fragmentation assay , drug cytotoxicity , drug effect , drug mechanism , DU 145 cancer cell line , enzyme assay , human , human cell , male , priority journal , prostate cancer cell line , protein determination , protein function , quantitative analysis , reverse transcription polymerase chain reaction , analogs and derivatives , apoptosis , biosynthesis , cell proliferation , cell survival , drug effects , drug potentiation , drug resistance , gene expression regulation , genetics , metabolism , pathology , Prostatic Neoplasms , tumor cell line