In:
Current Cancer Drug Targets, Bentham Science Publishers Ltd., Vol. 20, No. 8 ( 2020-09-04), p. 616-623
Kurzfassung:
Activation of PI3K/mTOR signaling pathway plays key role in the
progression of human osteosarcoma. Studies have confirmed that VS-5584 was a novel inhibitor of 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.
Materialart:
Online-Ressource
ISSN:
1568-0096
DOI:
10.2174/1568009620666200414150353
Sprache:
Englisch
Verlag:
Bentham Science Publishers Ltd.
Publikationsdatum:
2020
SSG:
15,3
