摘要
目的本文采用直接质谱(MS)法研究了乳腺癌荷瘤小鼠(Balb-c/EMT-6)不同生长周期代谢组学特征。方法小鼠(Balb-c)经过植入复苏传代后的肿瘤株(EMT-6)培养出荷瘤种鼠模型,转种于各实验周期组,在0、1、2、3和4周分别眼眶采血断颈处死;血样经预处理,制备出去蛋白的供试样品,经MS法分别检测出供试品的质谱图,记录各组分质荷比和离子强度;将整理后的不同周期所得质合比数据,代入组学专用软件SIMCA-P数据统计软件进行代谢物主成分分析,获得肿瘤组和空白组以及不同周期组之间的分散点图和负载点图。结果采用SIMCA-P软件计算出的荷瘤组和空白组分散点图有明显区分,各个周期组之间的分散点图存在良好的区分;由此获得负载图提取出与肿瘤生长密切相关的12个代谢组分,并初步鉴定出与糖代谢相关的1,3-二磷酸甘油酸、丙酮酸、乳酸、7-磷酸景天庚酮糖,琥珀酸、苹果酸;与核酸蛋白质等代谢相关的苯乳酸、5-甲基胞苷、次黄嘌呤核苷、磷酸胆碱和前列腺E2。结论小鼠乳腺癌生长过程中,除蛋白核酸合成活跃外,糖酵解代谢也表现出瓦博格效应的特征,提示肿瘤生长激活糖酵解产生的乳酸等代谢物将对肿瘤生长状态有潜在的指示作用。
Objective To investigate the metabonomics of mice breast cancer （Balb-c/EMT-6） in different growing periods, the directive mass spectrometry （MS） was applied. Methods The Balb/c-EMT-6 mice model was constructed by implanted the anabiotic EMT-6 tumor lines into the mice, and then the tumor was transferred to the test cycle groups. The blood was collected from orbit, and removed the tumor after putting to death by broken neck in 0, 1, 2, 3 and 4 week respectively. After the blood pre-treated to deprotein, the bio-samples were determined by the directive mass spectrometry respectively, then mass spectrum was recorded. The mated MS data of m/z and ion strength was analyzed with SIMCA-P, a professional statistic software of metabonomics, for principal component analysis. The scores scatter plot and loadings scatter plot between the blank and tumor groups and between different cycle groups were made. Results Holo-component analysis disclosed tumor and blank group had good discrimination and each group of the different period also had good discrimination. 12 endogenous metabolites were extracted from the loadings scatter plot, which related to tumor growth, and were identified. Some metabolites were related to glucose metabolism including 1,3-biphosphate glyceric acid, pyruvic acid, lactic acid, 7-phosphate D-sedoheptulose, succinic acid, malic acid and the others were related to protein and nucleic acid metabolism including phenyllactic acid,5-methylcytidine, carnine, phosphorylcholine, prostaglandin E2. Conclusion Addition to the activity of protein and nucleic acid synthesis, the glycolytic pathway also shown the characteristicst of Warburg effect in tumor growth process. It is informed that these increased metabolites will be a potential indicator of tumor growth status.
出处
《中国抗生素杂志》
CAS
CSCD
北大核心
2012年第8期637-640,I0001,I0004,共6页
Chinese Journal of Antibiotics
基金
四川省重点科技支撑项目(编号:2011SZ131 11-13 10.0)
关键词
乳腺癌
代谢组学
质谱法
Mice breast cancer
Metabolomics
MS
作者简介
康秋梅，女，生于1990年，在读硕士研究生，主要从事药物代谢分析，E-mail：kangqiumei007@163．com.
通讯作者，E—mail：xul06@sina．com
