MTH1 Inhibitor TH287 Suppresses Gastric Cancer Progress By Inducing Cell Apoptosis And G2/M Cell Cycle Arrest

Objective: To investigate the effect of MTH1 small molecule inhibitor TH287 on gastric cancer cells and further explore the potential mechanism of anti-gastric cancer.Methods: Gastric cancer cell lines BGC-823 and SGC-7901 were cultured in vitro and treated with different concentrations of MTH1 inhibitor TH287.Cell proliferation were detected by CCK-8 and cell clone formation assay.The effect of T H287 on the migration ability of BGC-823 cells and SGC-7901 cells were detected by scratch assay and Transwell assay.Apoptosis was determined by flow cytometry and mitochondrial membrance potential.Cell cycle was detected by flow cytometry.Bcl-2,Bax and PI3K/AKT signal pathway related protein were detected by Western blot.AKT phosphorylation activator SC79 pretreated gastric cancer cells to verify the effect of TH287 on the PI3K/AKT signal pathway.Results: The results of CCK-8 assay showed that TH287 inhibited BGC-823 cells and SGC-7901 cells in a concentration-and-time dependent manner(P<0.05).Clony formation assay results showed that the number of clone cells decreased with the increase concentration of TH287(P<0.05).Scratch and Transwell assay results showed that TH287 inhibited the ability of migration in BGC-823 cells and SGC-7901 cells(P<0.05).The results of Annexin-V/PI double staining and mito chondrial membrance potential assay showed that TH287 induced BGC-823 cells and SGC-7901 cells apoptosis(P<0.05)and mitochondrial membrance potential collapse(P<0.05).Cell cycle determination results showed that TH287 induced G2/M phase arrest in gastric cancer cells(P<0.05).The results of Western blot revealed that the ratio of Bcl-2/Bax and the level of PI3 K and p-AKT decreased after treated with TH287(P<0.05).After pretreated with AKT phosphorylation activat or SC79,TH287 decreased the inhibitory effect on gastric cancer cells,decreased apoptosis and increased cell ability.Conclusion:MTH1 inhibitor TH287 suppresses cell viability and cell proliferation of gastric cancer cells.In addition,TH287 can induce G2/M phase arrest.Moreover,TH287 can induce gastric cancer cells apoptosis via regulating PI3K/AKT pathway.