VS-5584 Inhibits Human Osteosarcoma Cells Growth by Induction of G1- phase Arrest through Regulating PI3K/mTOR and MAPK Pathways

Author(s): Jing-Yi Sun, Ya-Jun Hou, Hai-Juan Cui, Cheng Zhang, Ming-Feng Yang, Feng-Ze Wang, Zheng Sun, Cun-Dong Fan*, Bao-Liang Sun*, Jin Rok Oh*

Journal Name: Current Cancer Drug Targets

Volume 20 , Issue 8 , 2020


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Graphical Abstract:


Abstract:

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.

Keywords: VS-5584, osteosarcoma, G1-phase arrest, PI3K/mTOR, MAPK, cytotoxicity.

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Article Details

VOLUME: 20
ISSUE: 8
Year: 2020
Published on: 14 April, 2020
Page: [616 - 623]
Pages: 8
DOI: 10.2174/1568009620666200414150353
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