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Li-Qiang Zhi, Yi-Xin Yang, Shu-Xin Yao, Zhong Qing, Jian-Bing Ma
(Department of Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China (mainland))
Med Sci Monit 2018; 24:5914-5924
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.