Effects of COX-2 inhibitor Mavacoxib on proliferation, apoptosis and related signaling pathways of human osteosarcoma stem cells

LV Huicheng; JIA Haisheng; MA Min; WANG Mingbo; WU Yimin

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). Mean?while, 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?100μmol/L, Mavacoxib could improve the proliferation inhibition rates of osteosarco?ma stem cells in a dose and time dependent manner with statistical significant difference( P<0?05) . Compared with 0μmol/L, the ap?optotic 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 de?creased( P<0?05) . Conclusion Mavacoxib has toxic effect on human osteosarcoma stem cells, and can induce apoptosis and cell cy?cle arrest and inhibit the activation of Wnt/β?catenin and PI3K/Akt signaling pathway.