Abstract

Purpose
To identify the anti-cancer effect and investigate the underlying mechanism of MPS1/TTK (Monopolar spindle 1; also known as threonine tyrosine kinase) inhibitor in gastric cancer (GC) cell lines.
Materials and Methods
This study used compound-9, a highly selective MPS1/TTK inhibitor, to evaluate its anticancer effects on GC cell lines. Cell viability assay was performed to determine sensitivity to the inhibitor. Cell cycle analysis and apoptosis assays were performed using Flow cytometry to evaluate the effects of the inhibitor. Protein-expression levels were analyzed through western blotting after the inhibitor treatment.
Results
The EBV and MSI-H groups tended to be sensitive to the inhibitor, while the GS-likely group tended to be moderate-to-resistant. In contrast, the CIN-likely group was extremely sensitive or resistant. Within the CIN group, TP53^WT cell lines were sensitive, whereas TP53^MUT cell lines were sensitive or resistant. Upon treatment of the inhibitor, the TP53^WT-sensitive cell line underwent cell death more rapidly compared to the TP53^MUT-sensitive cell line. In contrast, the TP53^MUT-sensitive cell experienced higher levels of aneuploidy or polyploidy and underwent cell death at later time point than the TP53^WT-sensitive cell line. The TP53^MUT-resistant line can tolerate aneuploidy or polyploidy and exhibits drug resistance.
Conclusion
Our study explores the potential of an MPS1/TTK inhibitor, compound-9, as a targeted therapy in gastric cancer cells and investigates its mechanism of action.

• Keywords: Stomach Neoplasms, Chromosome instability, MPS1 inhibitor, SAC pathway