Anti-melanoma activity of Forsythiae Fructus aqueous extract in mice involves regulation of glycerophospholipid metabolisms by UPLC/Q-TOF MS-based metabolomics study.
Anti-melanoma activity of Forsythiae Fructus aqueous extract in mice involves regulation of glycerophospholipid metabolisms by UPLC/Q-TOF MS-based metabolomics study.
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DOI：
10.1038/srep39415
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发表时间：
2016-12-19
影响因子：
4.6
通讯作者：
He C
中科院分区：
文献类型：
--
作者：
Bao J;Liu F;Zhang C;Wang K;Jia X;Wang X;Chen M;Li P;Su H;Wang Y;Wan JB;He C
代谢组学是在整体背景下对生物系统的内源性代谢产物进行全面评估。在这项研究中，我们评估了连翘水提取物（FAE）的体内抗黑色素瘤活性，并全面探索了B16-F10黑色素瘤荷瘤小鼠的血清代谢组学特征。采用UPLC/Q-TOF MS结合模式识别方法来检查综合代谢特征和区分代谢物。结果表明，FAE对C57 BL/6小鼠B16-F10黑色素瘤具有显著的抗肿瘤活性，并恢复了肿瘤损伤引起的代谢紊乱。我们鉴定了17种与FAE抗肿瘤作用相关的代谢产物。这些代谢物中的大多数参与甘油磷脂代谢。值得注意的是，几种溶血磷脂酰胆碱（LysoPCs）在肿瘤模型组中显著降低，而FAE治疗使这些磷脂的变化恢复至接近正常状态。此外，我们发现溶血磷脂酰胆碱酰基转移酶1（LPCAT 1）和自分泌运动因子（ATX）在黑色素瘤中高表达，FAE显着下调其表达。这些结果表明，调节甘油磷脂代谢可能在黑色素瘤的生长和FAE的抗肿瘤活性中起着关键作用。此外，我们的研究结果表明，血清LysoPCs可能是黑色素瘤和其他恶性肿瘤的诊断和预后的潜在生物标志物。
Metabolomics is a comprehensive assessment of endogenous metabolites of a biological system in a holistic context. In this study, we evaluated the in vivo anti-melanoma activity of aqueous extract of Forsythiae Fructus (FAE) and globally explored the serum metabolome characteristics of B16-F10 melanoma-bearing mice. UPLC/Q-TOF MS combined with pattern recognition approaches were employed to examine the comprehensive metabolic signatures and differentiating metabolites. The results demonstrated that FAE exhibited remarkable antitumor activity against B16-F10 melanoma in C57BL/6 mice and restored the disturbed metabolic profile by tumor insult. We identified 17 metabolites which were correlated with the antitumor effect of FAE. Most of these metabolites are involved in glycerophospholipid metabolisms. Notably, several lysophosphatidylcholines (LysoPCs) significantly decreased in tumor model group, while FAE treatment restored the changes of these phospholipids to about normal condition. Moreover, we found that lysophosphatidylcholine acyltransferase 1 (LPCAT1) and autotaxin (ATX) were highly expressed in melanoma, and FAE markedly down-regulated their expression. These findings indicated that modulation of glycerophospholipid metabolisms may play a pivotal role in the growth of melanoma and the antitumor activity of FAE. Besides, our results suggested that serum LysoPCs could be potential biomarkers for the diagnosis and prognosis of melanoma and other malignant tumors.
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影响因子：
5.3
作者：
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