| Deoxynivalenol?DON?is a type B trichothecene mycotoxin colloquially known as“vomitoxin”,because of its emetic effects to pigs.DON is rapidly eliminated in animals without accumulation.DON has a wide range of cytotoxic effects,such as inducing DNA damage,increasing mitochondrial permeability;inhibiting the synthesis of macromolecules,but the impact and mechanism of DON on tumor were rarely reported.Using two tumor cells,WM793 and HCT116,we explored the effects and mechanism of DON on cell migration of tumor cells,and achieved the following results.1.MTT assay showed that the IC50 of DON to WM793 and HCT116 cells are 2.28?g/ml and 14.7?g/ml,respectively?2.Wound healing assay and soft agar colony formation assay suggested low dosage of DON can significantly inhibit tumor cell migration and tumor cell tumorigenicity,Indiciting DON may be a potentical candidate for anti-tumor drugs.3.Gene expression analysis showed that DON exposure significantly decreased the mRNA and protein level of tumor endothelial marker TEM8 in WM793 and HCT116 cells.DON treatment has comparable ability of cell migration inhibition to TEM8 knock-down cells.Overexpression of TEM8 can obviously relieve migration inhibition caused by DON.4.Further studies showed that DON significantly upregulated H3K27me3,and H3K27me3 was enriched in TEM8 promoter region.H3K27me3 inhibitor could reverse the inhibition of TEM8 expression and cell migration inhibition by DON,Suggesting one of the mechanisms of DON Inhibitting tumor cell migration is promoting H3K27me3,thereby inhibiting TEM8 expression.In summary,we found that DON can significantly inhibit the cell migration of two tumor cells,WM793 and HCT116.One of the mechanisms is promoting H3K27me3,thereby inhibiting TEM8 expression.It's the first time exploring the antitumor effect of DON,which provided some theoretical foundation for developping DON as an anticancer drug candidate. |
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