Abstract:

Objective To explore the effects of COX-2 inhibitor Mavacoxib on proliferation， apoptosis and related signaling pathways of human osteosarcoma stem cells. Methods The MG-63 cells were cultured in vitro to obtain osteosarcoma stem cells. The MTT assay was used to detect the proliferation inhibition rates after treatment with Mavacoxib（0， 1， 10， 50， 100 μmol/L）. Meanwhile， Annexin-FITC/PI double staining and PI staining were used to detect the apoptotic rates at 24， 48 h and cell cycle at 48 h after different concentrations of Mavacoxib. The effects of Mavacoxib on the Wnt/β-catenin and PI3K/Akt signaling pathway were measured by Western blotting. Results In the range of 10-100 μmol/L， Mavacoxib could improve the proliferation inhibition rates of osteosarcoma stem cells in a dose and time dependent manner with statistical significant difference（P＜0.05）. Compared with 0 μmol/L， the apoptotic rates and the percentage of G0/G1 phase cells were increased， the proportions of S phase and G2/M phase were decreased in other concentrations（P＜0.05）. After the treatment of Mavacoxib， the levels of PTEN in the PI3K/Akt pathway were increased， the levels of Akt in the PI3K/Akt pathway and the levels of β-catenin， C-myc and Cyclin D1 in the Wnt/β-catenin pathway were decreased（P＜0.05）.Conclusion Mavacoxib has toxic effect on human osteosarcoma stem cells， and can induce apoptosis and cell cycle arrest and inhibit the activation of Wnt/β-catenin and PI3K/Akt signaling pathway.