薏苡仁油抑制三阴性乳腺癌生长的代谢组学研究  

Metabonomics study of coix seed oil on suppressing the growth of triple negative breast cancer

作　　者：方婷 蒋义鑫 陈龙 柳润辉[1,4] 章丹丹 FANG Ting;JIANG Yixin;CHEN Long;LIU Runhui;ZHANG Dandan(School of Pharmacy,Fujian University of Traditional Chinese Medicine,Fujian 350122,China;Institute of Interdisciplinary Integrative Medicine Research,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Experiment Center of Science and Technology,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;School of Pharmacy,The Second Military Medical University,Shanghai 200433,China)

机构地区：[1]福建中医药大学药学院,福建福州350122 [2]上海中医药大学交叉科学研究院,上海201203 [3]上海中医药大学科技实验中心,上海201203 [4]海军军医大学药学院,上海200433

出　　处：《上海中医药杂志》2020年第2期78-84,共7页Shanghai Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(81773946,81573673,81001666).

摘　　要：目的基于LC-MS考察薏苡仁油干预三阴性乳腺癌原位荷瘤小鼠肿瘤生长的代谢组学情况。方法建立乳腺癌原位荷瘤小鼠模型,随机分为正常对照组、模型组和薏苡仁油给药组,薏苡仁油给药组灌胃给予薏苡仁油(7.5 mL·kg-1·d-1),连续灌胃给药14 d后,处死小鼠,取瘤组织并保留各组血清。HPLC-LTQ-Orbitrap Elite液质联用技术检测各组小鼠血清中的代谢变化并鉴定差异性代谢物。结果薏苡仁油显著抑制4T1乳腺癌细胞的体内生长(P<0.05),正常对照组、模型组及薏苡仁油给药组小鼠的血清代谢产物呈现不同的分布,通过正交偏最小二乘法-判别分析(OPLS-DA),找到正常对照组和模型组、模型组与薏苡仁油给药组,分别比较组间变量权重(VIP)均>1、P<0.05的差异代谢物。与正常组比较,有16种代谢物在模型组显著变化,包括孕烷三醇、溶血磷脂[18∶3(9Z,12Z,15Z)]、溶血磷脂乙醇[0∶0/22∶6(4Z,7Z,10Z,13Z,16Z,19Z)]、溶血磷脂[22∶5(7Z,10Z,13Z,16Z,19Z)]、溶血磷脂[22∶4(7Z,10Z,13Z,16Z)]、丙酮酸、2,6-二氨基-4-羟基-5-N-甲基甲酰胺基嘧啶、N-乙酰基-L-苯丙氨酸、十七烷酸、油酸、硬脂酸、花生四烯酸、二高-γ-亚麻酸、乙酸视黄酯、6-羟基-5-甲氧基吲哚葡糖苷酸、1-硬脂酰基-sn-甘油-3-磷酸乙醇胺,其中代谢物N-乙酰基-L-苯丙氨酸水平提高,其他代谢物水平降低,并在薏苡仁油给药后这些差异代谢物均有显著回调趋势(P<0.05)。结论薏苡仁油可能通过调控三阴性乳腺癌小鼠体内的花生四烯酸代谢、不饱和脂肪酸的生物合成、戊糖和葡萄糖醛酸的相互转化以及丙酮酸代谢等途径发挥抗肿瘤作用。Objective To study the metabonomics of coix seed oil intervention on tumor growth in tripe negative breast cancer 4T1-bearing mice based on LC-MS.Methods Orthotopic xenograft of 4T1 was established and randomly divided into control group,model group and coix seed oil administration group(7.5 m L/kg/d of Coix seed oil was given by gavage).After 14 days of administration,the mice in each group were executed to take tumor tissue and serum.HPLC-LTQ-Orbitrap Elite LC/MS was used to detect metabolic changes in the serum of each group of mice and identify differential metabolites.Results Coix seed oil significantly inhibited the growth of 4T1 in vivo(P<0.05).The levels of serum metabolites in normal mice,model mice and mice treated with coix seed oil showed different distributions.By orthogonal partial least squares-discriminant analysis(OPLSDA),the differential metabolite was selected by VIP values>1 among control group,the model group and the coix seed oil administration group(P<0.05).Compared with the normal group,16 metabolites changed significantly in the model group,including pregnanetriol,Lyso PC[18∶3(9Z,12Z,15Z)],lysophosphatidylethanolamine[0∶0/22∶6(4Z,7Z,10Z,13Z,16Z,19Z)],Lyso PC[22∶5(7Z,10Z,13Z,16Z,19Z)],Lyso PC[22∶4(7Z,10Z,13Z,16Z)],Pyruvic acid,2,6-diamino-4-hydroxy-5-(N-methylformamido)pyrimidine,N-Acetyl-L-phenylalanine,Margaric acid,Oleic acid,Stearic acid,Arachidonic acid,Dihomo-gamma-linolenic acid,Retinyl acetate,6-hydroxy-5-methoxyindole glucuronide,1-stearoyl-snglycero-3-phosphoethanolamine,among which the metabolite N-Acetyl-L-phenylalanine increased,other metabolites decreased and these differential metabolites showed a significant correction trend after coix seed oil administration(P<0.05).Conclusion Coix seed oil may have an anti-tumor effect on mice bearing 4T1 tumor by regulating arachidonic acid metabolism,biosynthesis of unsaturated fatty acids,mutual conversion of pentose and glucuronic acid and pyruvate metabolism.

关 键 词：薏苡仁油 非靶向代谢组学 三阴性乳腺癌 花生四烯酸代谢 

分 类 号：R285.5[医药卫生—中药学]