Inhibition of oleandrin on the proliferation show and invasion of osteosarcoma cells in vitro by suppressing Wnt/beta-catenin signaling pathway.

Article Details

Citation

Ma Y, Zhu B, Liu X, Yu H, Yong L, Liu X, Shao J, Liu Z

Inhibition of oleandrin on the proliferation show and invasion of osteosarcoma cells in vitro by suppressing Wnt/beta-catenin signaling pathway.

J Exp Clin Cancer Res. 2015 Oct 6;34:115. doi: 10.1186/s13046-015-0232-8.

PubMed ID
26444270 [ View in PubMed
]
Abstract

BACKGROUND: Osteosarcoma (OS) is a high-grade bone sarcoma with early metastasis potential, and the clinical chemotherapy drugs that are currently used for its treatment have some limitations. Recently, several studies have reported the selective antitumor effect of oleandrin on various tumor cells. In this study, we aimed to evaluate the effects and underlying mechanisms of oleandrin on OS cells. METHODS: The effect of oleandrin on the proliferation, morphology, and apoptosis of U2OS and SaOS-2 cells were analyzed in vitro. The activity of the Wnt/beta-catenin signaling pathway was determined using a dual luciferase assay. Semi-quantitative RT-PCR and western blot assays were performed to evaluate the mRNA and total protein expression of the downstream target genes. Changes of beta-catenin in intracellular localization were also explored using a western blot after separating the nucleus and cytoplasm proteins. The MMP-2 and MMP-9 enzymatic activities were determined using gelatin zymography. RESULTS: Oleandrin significantly inhibited the proliferation and invasion of OS cells in vitro, and induced their apoptosis. After treatment with oleandrin, the TOP/FOP flash ratio in OS cells was noticeably decreased, which indicated that the Wnt/beta-catenin signaling pathway was repressed. The expression of related Wnt target genes and total beta-catenin was downregulated, and a reduced nuclear beta-catenin level by oleandrin was observed as well. In addition, oleandrin suppressed the activities of MMP-2 and MMP-9. CONCLUSIONS: Oleandrin, in vitro, exerted a strong antitumor effect on human OS cells by suppressing the Wnt/beta-catenin signaling pathway, which interfered with the proliferation and invasion of OS cells, as well as induced cells apoptosis. Moreover, the expression and activities of MMP-2 and MMP-9 were downregulated by oleandrin, which contributed to the cells' lower invasiveness.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
Oleandrin72 kDa type IV collagenaseProteinHumans
Unknown
Inhibitor
Downregulator
Details
OleandrinMatrix metalloproteinase-9ProteinHumans
Unknown
Inhibitor
Downregulator
Details