Anticancer effects of zinc ion-mediated DNA demethylation in oesophageal squamous cell carcinoma.

BACKGROUND

Abnormalities in trace elements and the incidence of oesophageal squamous cell carcinoma (ESCC) have been reported in China. Zinc ions (Zn) are known to regulate DNA methylation by stabilizing methylase activity. However, the relationship between DNA methylation and Zn dysregulation in ESCC cells remains unclear. In this study, we examined changes in the biological behavior of ESCC cells treated with or without Zn.

METHODS

Biological behaviour changes in ESCC cells treated with or without Zn were analysed. Differences in the methylome and transcriptome of Zn-treated cells were determined by reduced representation bisulfite sequencing and RNA sequencing. An MTT cell viability assay was used to evaluate the cytotoxicity of cisplatin combined with Zn.

RESULTS

Zn can inhibit the malignant biological behaviour of ESCC cells. CpG methylation levels of promoter regions were decreased after Zn treatment in both ESCC and control cells. The degree of DNA methylation of genes encoding the metal ion-binding factors MT1E, MT1H and MT1X was significantly decreased, but their RNA expression levels were significantly increased after Zn treatment. Zn may enhance the expression of metallothioneins (MTs) via positive feedback through methylation regulation mechanisms. assays showed that the IC50 of Zn in ESCC cells was significantly lower than that in cells treated with cisplatin alone. In addition, ECa patients with high MT1E expression had a better prognosis.

CONCLUSION

Zn can reduce the methylation level and malignant biological behaviour of ESCC cells. The combination of Zn and cisplatin increases ESCC inhibition. Further study of MTs as biomarkers and targets in ESCC is warranted.