Li Xuan, Dai Jianguo, Tang Yongjun, Li Lulu, Jin Gang
School of Applied Chemistry and Biotechnology, Shenzhen Polytechnic, No. 2190 Liuxian Road, Nanshan District, Shenzhen 518055, Guangdong, China.
Mar Drugs. 2017 Jan 18;15(1):20. doi: 10.3390/md15010020.
Tachyplesin I is a cationic peptide isolated from hemocytes of the horseshoe crab and its anti-tumor activity has been demonstrated in several tumor cells. However, there is limited information providing the global effects and mechanisms of tachyplesin I on glioblastoma multiforme (GBM). Here, by using two complementary proteomic strategies (2D-DIGE and dimethyl isotope labeling-based shotgun proteomics), we explored the effect of tachyplesin I on the proteome of gliomaspheres, a three-dimensional growth model formed by a GBM cell line U251. In total, the expression levels of 192 proteins were found to be significantly altered by tachyplesin I treatment. Gene ontology (GO) analysis revealed that many of them were cytoskeleton proteins and lysosomal acid hydrolases, and the mostly altered biological process was related to cellular metabolism, especially glycolysis. Moreover, we built protein-protein interaction network of these proteins and suggested the important role of DNA topoisomerase 2-alpha (TOP2A) in the signal-transduction cascade of tachyplesin I. In conclusion, we propose that tachyplesin I might down-regulate cathepsins in lysosomes and up-regulate TOP2A to inhibit migration and promote apoptosis in glioma, thus contribute to its anti-tumor function. Our results suggest tachyplesin I is a potential candidate for treatment of glioma.
鲎素I是一种从鲎血细胞中分离出的阳离子肽，其抗肿瘤活性已在多种肿瘤细胞中得到证实。然而，关于鲎素I对多形性胶质母细胞瘤（GBM）的整体影响和机制的信息有限。在此，我们通过使用两种互补的蛋白质组学策略（二维差异凝胶电泳和基于二甲基同位素标记的鸟枪法蛋白质组学），探究了鲎素I对胶质瘤球蛋白质组的影响，胶质瘤球是由GBM细胞系U251形成的三维生长模型。总共发现192种蛋白质的表达水平在鲎素I处理后发生了显著变化。基因本体（GO）分析表明，其中许多是细胞骨架蛋白和溶酶体酸性水解酶，变化最大的生物学过程与细胞代谢有关，尤其是糖酵解。此外，我们构建了这些蛋白质的蛋白质-蛋白质相互作用网络，并表明DNA拓扑异构酶2-α（TOP2A）在鲎素I的信号转导级联反应中起重要作用。总之，我们提出鲎素I可能下调溶酶体中的组织蛋白酶并上调TOP2A，以抑制胶质瘤的迁移并促进其凋亡，从而有助于其抗肿瘤功能。我们的结果表明鲎素I是治疗胶质瘤的潜在候选药物。
