Tizanidine (Hydrochloride) Inhibits A549 Lung Cancer Cell Proliferation and Motility Through Regulating Nischarin

• Published in: OncoTargets and therapy 2020-01, Vol.13, p.291-298
• Main Authors: Zhao, Liang, Zhao, Gefei, Xue, Qi
• Format: Article
• Language: English
• Subjects: Analysis; Apoptosis; Cancer metastasis; Cholecystokinin; Computational biology; EDTA; Lung cancer; Novels; Original Research; Proteins; Tizanidine; Tumors
• ISSN: 1178-6930; 1178-6930
• DOI: 10.2147/OTT.S228317

Tizanidine hydrochloride (TZN) is a centrally acting α -adrenergic agonist. In this study, we aimed to explore the role of TZN on human lung cancer and to elucidate its underlying mechanisms. The effect of TZN treatment in A549 cell proliferation, migration, invasion and apoptosis was evaluated by CCK8, transwell and flow cytometer assays. The expression of apoptosis-related proteins and the activation of AKT and Wnt3a/β-catenin pathways were detected by Western blot. From the data of DrugBank, TZN could act as an agonist to target Nischarin in humans. We next investigated the function of Nischarin receptor in lung cancer and its role in the anti-tumor activity of TZN. The treatment of TZN inhibited the proliferation, migration and invasion of A549 cells, and induced apoptosis. These results were further confirmed by that TZN treatment increased the Bax/Bcl-2 ratio in A549 cells. We also observed that TZN treatment changed the expression and phosphorylation of proteins of AKTand Wnt3a/β-catenin signaling pathway members. By bioinformatics analysis, we found that Nischarin was down-regulated in human lung cancer tissues and patients with high Nischarin expression had a better survival. Moreover, Nischarin functioned as a tumor suppressor in the survival and metastasis of A549 cells through the regulation of AKT and Wnt3a/β-catenin pathways. Knockdown of Nischarin promoted the proliferation, invasion, migration of A549 cells and inhibited the apoptosis, which were reversed by the TZN treatment. Summary, our data revealed that treatment of TZN inhibited the growth of lung cancer cell line A549 and may be used as a novel strategy for lung cancer therapy.