Title:VS-5584 Inhibits Human Osteosarcoma Cells Growth by Induction of G1- phase Arrest through Regulating PI3K/mTOR and MAPK Pathways
Volume: 20
Issue: 8
关键词:
VS-5584,骨肉瘤,G1期阻滞,PI3K / mTOR,MAPK,细胞毒性。
摘要:
Background: Activation of the PI3K/mTOR signaling pathway plays a key role in the
progression of human osteosarcoma. Studies have confirmed that VS-5584 was a novel inhibitor of
the PI3K/mTOR pathway, and displayed potential anticancer activity.
Objective: To explore the anticancer effect and underlying mechanism of VS-5584 against the
growth of human osteosarcoma cells.
Methods: U2OS and MG-63 human osteosarcoma cells were cultured and the cytotoxicity, cell
apoptosis in VS-5584-treated cells were explored by the CCK8 assay, flow cytometric analysis and
western blot. Cell migration and tube formation were also employed to examine the anticancer potential.
Results: The results showed that VS-5584 treatment dose-dependently inhibited the growth of U2OS
and MG-63 cells by induction of G1-phase arrest through regulating p21, p27, Cyclin B1 and Cdc2.
Further investigation revealed that VS-5584 treatment effectively inhibited the PI3K/mTOR signaling
pathway and triggered MAPK phosphorylation. Moreover, VS-5584 treatment dramatically suppressed
cell migration and tube formation of HUVECs, followed by the down-regulation of HIF-1α
and VEGF.
Conclusion: Our findings validated that VS-5584 may be a promising anticancer agent with potential
application in the chemotherapy and chemoprevention of human osteosarcoma.