微量元素硒联合环磷酰胺抗小鼠白血病的实验研究  

Antileukemia Effects of Cyclophosphamide Combined with Selenium on P388 Leukemia Mice

作　　者：谈立[1] 张学梅[2] 李忠忠[1] 马海英[1] 

机构地区：[1]中国医科大学附属第四医院药学部,沈阳110032 [2]中国医科大学附属第四医院肿瘤科,沈阳110032

出　　处：《中国医科大学学报》2010年第10期834-837,共4页Journal of China Medical University

摘　　要：目的研究微量元素硒联合环磷酰胺对P388小鼠白血病的抗癌效果,探讨微量元素硒在治疗白血病过程中的作用及其分子机制。方法采用含硒化合物联合环磷酰胺治疗P388小鼠白血病模型,通过观察荷瘤小鼠的生存期判断其抑癌效果。采用原位杂交和免疫细胞化学技术检测淋巴细胞中的bcl-2基因的表达,利用流式细胞术检测细胞凋亡、增殖指数及细胞周期。通过检测动物体内抗氧化水平指标超氧化物歧化酶、丙二醛和谷胱甘肽,判定硒化合物的保护作用。结果含硒化合物尤其是有机含硒化合物联合环磷酰胺能够使荷瘤小鼠的生存期延长,bcl-2基因表达下调,细胞凋亡指数增高,机体抗氧化水平升高,与对照组比较有统计学差异(P<0.05)。结论微量元素硒联合抗肿瘤化疗药物后对肿瘤治疗具有协同作用,能显著抑制癌细胞的增殖,下调bcl-2基因的表达,诱导癌细胞的凋亡,延长荷瘤小鼠的生存期。Objective To investigate the antileukemia effect of cyclophosphamide combined with selenium on P388 leukemia mice.To explore the molecular mechanism of selenium in the process that treats leukaemia.Methods The P388 leukemia mice models were administrated with cyclophosphamide combined with selenium.In situ hybridization and immunoeytoehemistry assay were used to detect the expression of bcl-2 gene.Flow cytometry was used to assess the extent of cell apoptosis,proliferation index and cell cycle.The effect of antileukemia was determined by observing the life span of P388 beating mice,and the protective effect of selenium compounds on tumor-bearing mice were evaluated by antioxidant indices（superoxide dismutase,glutathione and methylene dioxyamphetamine）.Results Selenium compounds,especially methylselenocysleine combined with cyclophosphamide prolonged the life span of tumor-bearing mice,downregulated markedly the expression of bcl-2 gene,and increased apoptosis index and improved the antioxidant level in vivo on statistics （P 〈 0.05）.Conclusion Combination of cyclophosphamide and selenium markedly enhanced the antileukemia effect and downregulated the expression of bcl-2 gene and induced the cancer cell apoptosis,prolonged the life span of P388 tumor-bearing mice.

关 键 词：硒 环磷酰胺 小鼠 白血病 

分 类 号：R965[医药卫生—药理学]