目的考察海洋生物活性碱fascaplysin对肝癌细胞Bel-7402代谢物的影响。方法利用超高效液相色谱-四极杆-飞行时间质谱,采用电喷雾电离源分别在正负离子模式下,对通过fascaplysin处理4、12和24 h的Bel-7402的乙腈提取物进行分析,并通过SIMCA-P软件进行主成分分析和正交偏最小二乘法辨别分析。结果12 h后fascaplysin处理组能够与对照组在PCA得分图上完全区分开,24 h后两组处理则显著分开。分析fascaplysin作用Bel-7402细胞后的潜在代谢标志物,发现主要为磷脂酰乙醇胺、磷脂酰胆碱、鞘磷脂、脂肪酰胺、植物鞘氨醇、二氢神经鞘氨醇、二甲基鞘氨醇、N-Palmitoyl Taurine和N-oleoylTaurine。结论鞘磷脂的下调以及磷脂酰胆碱、植物鞘氨醇、二氢神经鞘氨醇、二甲基鞘氨醇的上调表明胞内鞘磷脂途径被激活可能是fascaplysin引起细胞凋亡的一种作用机制。
OBJECTIVE To study the effect of marine bioactive alkaloid fascaplysin on metabolites of hepatocellular carcinoma cell line BeL-7402.METHODS Acetonitrile extract from BeL-7402 cells was treated with fascaplysin for 4,12,24 h and was studied by ultra performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF-MS) using electron spraying ionization with positive and negative mode.Principle component analysis(PCA) and orthogonal-projection to latent structures discriminant analysis(O-PLS-DA) were built using the SIMCA-P to separate the control treatment and drug treatment and to find compounds expressed in significantly different amounts between the two populations.RESULTS Fascaplysin-treated group and control group were be totally separated after 12 h on the PCA score plot,and be significantly separated after 24 h.Most of the potential biomarkers were identified as phosphatidylenthanolamine,phosphatidylcholine,sphingomyeline,fatty amide,phosphatidylcholine,sphinganine,N,N-dimethyl-safingol and phytosphingosine.CONCLUSION Down-regulation of sphingomyeline and up-regulation of phosphatidylcholine,sphinganine,N,N-dimethyl-safingol and phytosphingosine indicated that fascaplysin treatment might activate the sphingolipid signaling pathway.Apoptosis might be induced by fascaplysin,which was in agreement with the observation of fascaplysin-induced apoptosis on BeL-7402.