Department of Biochemistry, Gyeongsang National University School of Medicine, and Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Korea.
Department of Urology, Gyeongsang National University Hospital, and Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Korea.
BMB Rep. 2017 Sep;50(9):466-471. doi: 10.5483/bmbrep.2017.50.9.087.
The results of this study show that c-Jun N-terminal kinase (JNK) activation was associated with the enhancement of docetaxel-induced cytotoxicity by simvastatin in DU145 human prostate cancer cells. To better understand the basic molecular mechanisms, we investigated simvastatin-regulated targets during simvastatin-induced cell death in DU145 cells using two-dimensional (2D) proteomic analysis. Thus, vimentin, Ras-related protein Rab-1B (RAB1B), cytoplasmic hydroxymethylglutaryl-CoA synthase (cHMGCS), thioredoxin domain-containing protein 5 (TXNDC5), heterogeneous nuclear ribonucleoprotein K (hnRNP K), N-myc downstream-regulated gene 1 (NDRG1), and isopentenyl-diphosphate Delta-isomerase 1 (IDI1) protein spots were identified as simvastatin-regulated targets involved in DU145 cell death signaling pathways. Moreover, the JNK inhibitor SP600125 significantly inhibited the upregulation of NDRG1 and IDI protein levels by combination treatment of docetaxel and simvastatin. These results suggest that NDRG1 and IDI could at least play an important role in DU145 cell death signaling as simvastatinregulated targets associated with JNK activation. [BMB Reports 2017; 50(9): 466-471].
本研究结果表明，c-Jun N-末端激酶（JNK）的激活与辛伐他汀增强多西紫杉醇对 DU145 人前列腺癌细胞的细胞毒性有关。为了更好地了解基本的分子机制，我们使用二维（2D）蛋白质组学分析研究了辛伐他汀诱导 DU145 细胞死亡过程中辛伐他汀调节的靶点。因此，角蛋白中间丝相关蛋白 vimentin、Ras 相关蛋白 Rab-1B（RAB1B）、细胞质羟甲基戊二酰基辅酶 A 合酶（cHMGCS）、硫氧还蛋白结构域蛋白 5（TXNDC5）、异质核核糖核蛋白 K（hnRNP K）、N- 神经母细胞瘤下调基因 1（NDRG1）和异戊烯基二磷酸 Delta-异构酶 1（IDI1）蛋白斑点被鉴定为涉及 DU145 细胞死亡信号通路的辛伐他汀调节靶点。此外，JNK 抑制剂 SP600125 显著抑制了多西紫杉醇和辛伐他汀联合治疗时 NDRG1 和 IDI 蛋白水平的上调。这些结果表明，NDRG1 和 IDI 作为与 JNK 激活相关的辛伐他汀调节靶点，至少在 DU145 细胞死亡信号中发挥重要作用。[BMB 报告 2017；50(9): 466-471]。
