Sodium nitrite improves epithelial-mesenchymal transition of hepatoma cells in mice bearing H22 / 药学学报

ABSTRACT

This study is to report the determination of the effect of sodium nitrite induced oxygen species (ROS) on the epithelial-mesenchymal transition in hepatoma cells in mice bearing H22 and investigation of its role in hypoxia-inducible factor 1alpha (HIF-1alpha) in this process. Mice hepatocarcinoma cell line H22 was inoculated subcutaneously into right axillary of sixty male Kunming mice and then randomly divided into four groups control group; low-dose sodium nitrite group (10 mg x kg(-1)), medium-dose sodium nitrite group (20 mg x kg(-1)) and high-dose sodium nitrite group (30 mg x kg(-1)). Sodium nitrite group was given (ig) sodium nitrite with 10-30 mg x kg(-1) x d(-1) for 21 days. Compared with control group, there was no obvious difference between the two groups in the volume or weight of xenografts, but in sodium nitrite treatment group, the activity of SOD and CAT decreased and contents of MDA or nitrite increased in tumor tissue of mice bearing H22; epithelial-mesenchymal transition (EMT) of hepatoma cells was induced, the EMT-phenotype tumors displayed a greater degree of local aggressiveness, with dissection through adjacent fascia and skeletal muscle. The increased expression of HIF-la and vimentin and declination of E-cadherin were confirmed by immunohistochemistry and Western blotting. These data indicate sodium nitrite treatment could improve the epithelial-mesenchymal transition of xenografts in mice bearing H22, which might relate to the fact that ROS mediated signal pathway increased the expression of HIF-1alpha.