Sodium nitrite improves epithelial-mesenchymal transition of hepatoma cells in mice bearing H22.
- Author:
Hong-Rui XU
1
;
Bo LIN
;
Si-Qian WANG
;
Zhi ZHANG
;
Xiao-Xia LU
;
Yue LIU
;
Huang-Fu CHAO-SHEN
Author Information
1. Institute of Environmental Medicine, Medical College of Henan University, Kaifeng 475004, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Cadherins;
metabolism;
Carcinoma, Hepatocellular;
metabolism;
pathology;
Catalase;
metabolism;
Cell Line, Tumor;
Dose-Response Relationship, Drug;
Epithelial-Mesenchymal Transition;
drug effects;
Humans;
Hypoxia-Inducible Factor 1, alpha Subunit;
metabolism;
Liver Neoplasms;
metabolism;
pathology;
Male;
Malondialdehyde;
metabolism;
Mice;
Neoplasm Transplantation;
Random Allocation;
Reactive Oxygen Species;
metabolism;
Signal Transduction;
drug effects;
Sodium Nitrite;
administration & dosage;
pharmacology;
Superoxide Dismutase;
metabolism;
Tumor Burden;
drug effects;
Vimentin;
metabolism
- From:
Acta Pharmaceutica Sinica
2012;47(11):1470-1476
- CountryChina
- Language:Chinese
-
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.
