Department of Joint Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland).
Medical Experiment Center, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China (mainland).
Med Sci Monit. 2018 Aug 25;24:5914-5924. doi: 10.12659/MSM.909973.
BACKGROUND Osteosarcoma (OS) is a highly complicated bone cancer involving imbalance of signaling transduction networks in cells. Development of new anti-osteosarcoma drugs is very challenging, mainly due to lack of known key targets. MATERIAL AND METHODS In this study, we attempted to reveal more promising targets for drug design by "Target-Pathway" network analysis, providing the new therapeutic strategy of osteosarcoma. The potential targets used for the treatment of OS were selected from 4 different sources: DrugBank, TCRD database, dbDEMC database, and recent scientific literature papers. Cytoscape was used for the establishment of the "Target-Pathway" network. RESULTS The obtained results suggest that tankyrase 2 (TNKS2) might be a very good potential protein target for the treatment of osteosarcoma. An in vitro MTT assay proved that it is an available option against OS by targeting the TNKS2 protein. Subsequently, cell cycle and apoptosis assay by flow cytometry showed the TNKS2 inhibitor can obviously induce cell cycle arrest, apoptosis, and mitotic cell death. CONCLUSIONS Tankyrase 2 (TNKS2), a member of the multifunctional poly(ADP-ribose) polymerases (PARPs), could be a very useful protein target for the treatment of osteosarcoma.
骨肉瘤（OS）是一种高度复杂的骨癌，涉及细胞信号转导网络的失衡。开发新的抗骨肉瘤药物极具挑战性，主要是因为缺乏已知的关键靶点。
在这项研究中，我们试图通过“靶-途径”网络分析来揭示更有前途的药物设计靶点，为骨肉瘤提供新的治疗策略。用于治疗 OS 的潜在靶标从 4 个不同的来源中选择：DrugBank、TCRD 数据库、dbDEMC 数据库和最近的科学文献。Cytoscape 用于建立“靶-途径”网络。
结果表明，端锚聚合酶 2（TNKS2）可能是治疗骨肉瘤的一个非常好的潜在蛋白靶点。体外 MTT 测定证明，通过靶向 TNKS2 蛋白，它是一种针对 OS 的有效选择。随后，通过流式细胞术进行的细胞周期和凋亡检测显示，TNKS2 抑制剂可明显诱导细胞周期停滞、凋亡和有丝分裂细胞死亡。
多聚（ADP-核糖）聚合酶（PARPs）的多功能成员端锚聚合酶 2（TNKS2）可能是治疗骨肉瘤的非常有用的蛋白靶点。
