亚硝酸钠对H22荷瘤小鼠移植瘤上皮-间质转化的促进作用  

Sodium nitrite improves epithelial-mesenchymal transition of hepatoma cells in mice bearing H22

作　　者：徐红瑞[1] 林波 王思谦[1,2] 张挚[1] 路晓霞[1,2] 刘悦[1] 皇甫超申[1] 

机构地区：[1]河南大学医学院环境医学研究所,河南开封475004 [2]河南大学护理学院,河南开封475004

出　　处：《药学学报》2012年第11期1470-1476,共7页Acta Pharmaceutica Sinica

基　　金：国家重大环保公益项目专项(200809115);省部共建河南大学科研项目(SBGJ090702)

摘　　要：研究亚硝酸钠诱导活性氧对H22荷瘤小鼠肝癌细胞上皮间质转化和缺氧诱导因子1α(HIF-1α)的影响,并探讨HIF-1α在这一过程中的作用。制备H22肝癌细胞荷瘤小鼠模型,亚硝酸钠处理组每天分别灌胃给予10、20和30 mg.kg 1亚硝酸钠,对照组给予等体积生理盐水,连续给药21天。与对照组相比,亚硝酸钠处理组的移植瘤体积和重量没有明显变化,但是肿瘤组织内超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性下降,亚硝酸盐和丙二醛(MDA)含量升高;癌细胞浸润周围的肌肉和筋膜;免疫组化和Western blotting结果显示,细胞波形蛋白和HIF-1α表达增强,E-钙粘素表达下降;肿瘤细胞呈现出上皮间质转化(EMT)。结果提示,亚硝酸钠在体内能够促进鼠肝癌细胞EMT发生,其机制与亚硝酸盐诱导活性氧(ROS)促进HIF-1α表达增加有关。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 la （HIF-la） 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＇kg-1）, medium-dose sodium nitrite group （20 mg.kg-1） and high-dose sodium nitrite group （30 mg.kg-1）. Sodium nitrite group was given （ig） sodium nitrite with 10-30 mg kg-1d-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- 1a.

关 键 词：亚硝酸盐 H22细胞 移植瘤 上皮间质转化 缺氧诱导因子1Α 

分 类 号：R965[医药卫生—药理学]