Degirmenci Mustafa, Erdogan Atike Pinar, Bulut Gulcan, Atmaca Harika, Uzunoglu Selim, Karaca Burcak, Karabulut Bulent, Uslu Ruchan
Department of Internal Medicine, School of Medicine, Tepecik Research and Education Hospital, Izmir, Turkey.
Department of Medical Oncology, School of Medicine, Ege University, Izmir, Turkey.
Tumour Biol. 2016 Apr;37(4):4939-44. doi: 10.1007/s13277-015-4331-0. Epub 2015 Nov 3.
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.
前列腺癌(PCa)是男性中最常见的癌症类型。尽管早期前列腺癌的生存率较高,但对于复发性疾病,治疗选择非常有限。在本研究中,在DU-145激素和药物难治性前列腺癌细胞系中研究了奥曲肽与AT-101联合使用可能产生的协同细胞毒性和凋亡作用。为了阐明联合治疗的作用机制,还研究了生长抑素受体2和5(SSTR2和SSTR5)的表达水平。通过XTT法测定细胞活力。通过DNA片段化分析和半胱天冬酶3/7测定评估细胞凋亡。分别通过qRT-PCR和蛋白质印迹分析评估SSTR2和SSTR5的mRNA和蛋白质水平。与单独使用任何一种药物相比,奥曲肽与AT-101联合使用可协同抑制DU-145细胞的活力并诱导其凋亡。联合治疗增加了DU-145细胞中SSTR2和SSTR5的mRNA和蛋白质水平。数据表明,这种联合疗法可能是对雄激素剥夺无反应的晚期转移性前列腺癌患者的良好候选方案。