Abstract
To investigate the inhibitory effect of indomethacin combined with imatinib on proliferation of KCL22 and K562/G01 cells, and to elucidate the molecular mechanism of antiproliferative effect by Wnt/β-Catenin signaling way. Indomethacin was used in KCL22 and K562/G01 cells. The cell growth was detected by MTT assay to explore the optimal concentration and time. The effect of drugs on proliferation capacity was assessed by MTT assay and colony-forming assay. Flow cytometry was used to identify the cell cycle and apoptosis changes. The protein expression of pβ-catenin (S33/37/T41), pGSK-3β (Ser9) and C-MYC were analyzed by Western blot. The optimal concentration and time of indomethacin on KCL22 and K562/G01 were 80 µmol/L for 48 h. The inhibitory effect of 80 µmol/L indomethacin combined 2 µmol/L imatinib on cell proliferation was significantly better than a single drug treatment. Flow cytometry results showed that cell cycle was arrested in the G0/G1 phase in both combined treatment groups. The number of apoptosis cells in combined treatment groups was significantly higher than that in single drug treatment groups. Compared with the control group or single drug treatment groups, the protein level of pβ-catenin, β-catenin, pGSK-3β (Ser9) and C-MYC decreased significantly. Indomethacin significantly enhances inhibitory effect of imatinib on proliferation of KCL22 and K562/G01 cells and regulate cell proliferation through Wnt/β-Catenin signaling way.
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