Knockdown of Notch-1 augments inhibitory effect of dihydroartemisinin on viability of human osteosarcoma cell line U-2OS

AIM: To investigate the effect of Notch-1 knockdown on the growth of dihydroartemisinin-inhibited human osteosarcoma cell line U-2OS. METHODS: U-2OS cells treated with different concentrations of dihydroartemisinin (5, 10, 15 and 20 μmol/L) were collected. The expression of Notch-1, MMP-2, MMP-9 and Hes-1 at mRNA and protein levels was measured by real-time PCR and Western blotting, respectively. U-2OS cells were transfected with Notch-1 siRNA for 24 h and incubated with dihydroartemisinin for another 24 h. The cell apoptotic rate, protein expression of MMP-2, MMP-9 and Hes-1, and the migration ability were measured by MTT assay, Western blotting and Transwell experiment, respectively. RESULTS: Dihydroartemisinin (5, 10, 15 and 20 μmol/L) decreased the expression of Notch-1, MMP-2, MMP-9 and Hes-1 at mRNA and protein levels in a dose-dependent manner. Down-regulation of Notch-1 significantly enhanced the effect of dihydroartemisinin on the cell apoptosis, the protein expression of MMP-2, MMP-9 and Hes-1, and migration ability (P<0.05). CONCLUSION: Notch-1 pathway is involved in the process of dihydroartemisinin-inhibited U-2OS cell growth. Knockdown of Notch-1 augments the inhibitory effect of dihydroartemisinin on U-2OS cell viability.