Reversine (Rev) has been used for the treatment of a number of cancers. However, there have been no previous reports for the use of Rev for gastric cancer (GC). The aim of the present study was to investigate the effect of Rev on cell proliferation, migration, invasion and cell apoptosis in human GC cells and TTK expression. Cell Counting Kit-8 and colony formation were used to assess cell proliferation. Wound healing and Transwell assays were performed to examine cell migration and invasion, respectively. Cell apoptosis was measured using TUNEL staining and western blotting. Reverse transcription-quantitative PCR and western blotting were performed to determine TTK expression in AGS and NCI-N87 GC cells. Rev treatment inhibited the viability of the two GC cells lines in a dose-dependent manner and suppressed their capacities of clone formation, migration and invasion. Rev-treated cells exhibited reduced matrix metalloproteinase (MMP)2/9 expression and increased apoptosis compared with those in control cells. In addition, expression of the anti-apoptotic protein Bcl-2 was significantly decreased, whilst the expression levels of the pro-apoptotic factors Bax and cleaved-caspase-3/9 were increased by Rev treatment compared with that in the control group that were not treated with Rev. In addition, TTK protein expression was decreased in cells treated with Rev compared with that in untreated cells. However, overexpression of TTK significantly reversed the aforementioned effects of Rev in GC cells. These results suggest that Rev may inhibit the proliferation, invasion and migration of GC cells whilst inducing cell apoptosis by suppressing TTK expression. Therefore, Rev may confer potential properties as a therapeutic anti-cancer agent. Additionally, TTK may serve as a molecular target for the treatment of gastric cancer.
Keywords: TTK; apoptosis; gastric cancer; migration; reversine.
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