Effects of Paris polyphylla ethanol extract on human osteosarcoma and its mechanism / 中草药

ABSTRACT

Objective To evaluate the potential anti-osteosarcoma effects of Paris polyphylla ethanol extract (PPEE) and investigate its underlying mechanisms. Methods The anti-proliferation activity of PPEE was tested on 143B, MG-63, U-2 OS, and hFOB1.19 cells using MTT assay. The pro-apoptotic and cell cycle arrest effects of PPEE were confirmed by Hoechst 33342 staining and flow cytometry. The anti-vasculogenic mimicry effects of PPEE were investigated by Matrigel culture assays. The related proteins expression was evaluated by Western blottig. Results PPEE evidently suppressed cell proliferation of 143B, MG-63, and U-2 OS cells with IC50 values of 10-60 μg/mL, but showed little cytotoxicity against normal osteoblastic cell. PPEE induced G2/M phase arrest associated with elevated phosphorylation of CDK1, Cdc25C, Chk2 and down-regulation of cyclin B1 expression. It also promoted apoptosis in 143B cells by up-regulating the expression of cleaved Caspase-3, Caspase-8, and Caspase-9, and Bax/Bcl-2 ratio. Additionally, PPEE inhibited 143B cells vasculogenic mimicry formation at non-cytotoxic concentrations through decreasing the expression of FAK, Mig-7, MMP-2, and MMP-9. Finally, four weeks’ daily oral administration of PPEE exhibited potent antitumor and anti-vasculogenic mimicry activity in 143B xenograft model with low toxicity. Conclusion These findings demonstrated that PPEE possesses anti-osteosarcoma and anti-vasculogenic mimicry activity in vitro and in vivo, and its underlying mechanisms may be related to inducing apoptosis, blocking cell cycle, and destroying vasculogenic mimicry formation of osteosarcoma cells. Therefore, PPEE is a potential candidate for osteosarcoma treatment.