NMR法研究小鼠乳腺癌生物标记物的代谢组学

Preliminary study of the metabonomics for bio-marks in mice breast cancer

目的用NMR法研究小鼠乳腺癌(Balb-c/EMT-6)不同生长周期中血清的代谢组学,寻找可能与肿瘤生长代谢相关的生物标记物。方法采集小鼠血清中代谢组分的NMR谱,对比小鼠乳腺癌肿瘤生长组(1～4周)与正常对照组代谢成分的变化,经绿原酸(CHA)治疗两周组的代谢物变化验证,结合PLS-DA模式识别分析,寻找小鼠乳腺癌肿瘤生长潜在的生物标志物。结果正常组与肿瘤生长组有明显的分离,肿瘤生长组中各周期组之间相互分离。两周CHA治疗组与正常组接近,但与肿瘤组明显分离。与正常组比较,肿瘤组的乳酸、乙酸和胆碱随肿瘤生长呈增加趋势,柠檬酸和肌酸的递增趋势较弱,而葡萄糖和脂蛋白(VLDL/LDL)随肿瘤生长有所减小。两周CHA治疗组与同期的肿瘤组比较,代谢关联组分发生明显变化(乳酸、胆碱和乙酸的量有所下降),与正常组基本接近。结论通过PLS-DA法提取出的乳酸、乙酸、胆碱等代谢组分与肿瘤生长具有一定相关性,可作为乳腺癌潜在的生物标志物的研究对象。

OBJECTIVE Serum metabonomics investigation on breast cancer beared rats（Balb-c/EMT-6）in different growth cycle was carried out using nuclear magnetic resonance（NMR）.The investigation was to search for the biological markers relative to tumor growth and Metabolism.METHODS NMR spectrum of the rats serum metabolite was collected to compare the metabolites in tumor group and control group,and identify the potential biological marker of the breast cancer in rats in combination with PLS-DA analysis.RESULTS Control group was apparently separated with tumor growth group,and separation was also achieved among tumor groups.After CHA treatment,the test group was near to control group,but separated from tumor group.Compared to the control,the levels of lactic acid,acetic acid and bilineurine increased in tumor group,and the levels of citric acid and creatine in tumor group increased less.However,the levels of glucose and VLDL/LDL in tumor group decreased with tumor growth.After CHA treatment for two weeks,the metabolites in test group was get close to control group.CONCLUSION The results indicated that these metabolites（lactic acid,acetic acid,and bilineurine so on）were associated with tumor growth to some extent and could be served as the potential bio-markers of breast cancer.