Tanpure Smita, Boyineini Jerusha, Gnanamony Manu, Antony Reuben, Fernández Karen S, Libes Jaime, Lin Julian, Pinson David, Joseph Pushpa A, Gondi Christopher S
Department of Internal Medicine, University of Illinois College of Medicine, Peoria, IL 61605, USA.
Department of Pediatrics, University of Illinois College of Medicine, Peoria, IL 61605, USA.
Oncol Lett. 2017 Jun;13(6):4602-4610. doi: 10.3892/ol.2017.6075. Epub 2017 Apr 24.
Neuroblastoma is the cause of >15% of cancer-associated mortality in children in the USA. Despite aggressive treatment regimens, the long-term survival rate for these children remains at <40%. The current study demonstrates that secreted protein acidic and rich in cysteine (SPARC) suppresses radiation-induced expression of heat shock protein 27 (HSP27) and suppresses mitochondrial membrane potential (Δψ) in neuroblastoma cells. In the present study, the overexpression of SPARC in SK-N-BE(2) and NB1691 neuroblastoma cell lines suppresses radiation-induced G2M cell cycle arrest, proliferation, HSP27 expression ( and ) and induces the collapse of the mitochondrial Δψ. Gene ontology analysis demonstrated that the overexpression of SPARC combined with irradiation, induces the expression of dissimilar molecular function genes in SK-N-BE(2) and NB1691 cells, providing evidence of a dissimilar response signaling pathway. These results demonstrate that overexpression of SPARC suppresses radiation-induced HSP27 expression in neuroblastoma cells and the combination of SPARC and radiation induces the expression of protein 21, but suppresses neuroblastoma tumor density in mouse models. SPARC also induces mitochondrial Δψ collapse in SK-N-BE(2) and NB1691 neuroblastoma cells.
神经母细胞瘤是美国儿童癌症相关死亡率超过15%的病因。尽管有积极的治疗方案，但这些儿童的长期生存率仍低于40%。当前研究表明，富含半胱氨酸的酸性分泌蛋白（SPARC）可抑制神经母细胞瘤细胞中辐射诱导的热休克蛋白27（HSP27）表达，并抑制线粒体膜电位（Δψ）。在本研究中，SPARC在SK-N-BE(2)和NB1691神经母细胞瘤细胞系中的过表达抑制了辐射诱导的G2M细胞周期阻滞、增殖、HSP27表达（以及），并诱导线粒体Δψ的崩溃。基因本体分析表明，SPARC过表达与辐射相结合，可诱导SK-N-BE(2)和NB1691细胞中不同分子功能基因的表达，为不同的反应信号通路提供了证据。这些结果表明，SPARC过表达可抑制神经母细胞瘤细胞中辐射诱导的HSP27表达，并且SPARC与辐射的联合可诱导蛋白21的表达，但在小鼠模型中可抑制神经母细胞瘤肿瘤密度。SPARC还可诱导SK-N-BE(2)和NB1691神经母细胞瘤细胞中的线粒体Δψ崩溃。
