脂质质谱成像揭示三氯生促进三维肝癌肿瘤细胞球增长的相关机理  

Mass Spectrometry Imaging Reveals Lipid Changes Associated with the Cell Proliferation of Liver Tumor Spheroids Treated with Triclosan

作　　者：陈静 谢佩斯 蔡宗苇 CHEN Jing;XIE Pei-si;CAI Zong-wei(College of Chemistry,Fuzhou University,Fuzhou 350108,China;State Key Laboratory of Environmental and Biological Analysis,Hong Kong Baptist University,Hong Kong 999077,China)

机构地区：[1]福州大学化学学院,福建福州350108 [2]香港浸会大学环境与生物分析国家重点实验室,中国香港999077

出　　处：《质谱学报》2023年第2期213-222,共10页Journal of Chinese Mass Spectrometry Society

基　　金：国家自然科学基金项目(22036001)。

摘　　要：三氯生(triclosan,TCS)作为一种广谱抗菌剂被广泛应用于多种日常消费品中。当前研究表明,TCS暴露可以促进肝癌肿瘤增长,但涉及的相关脂质代谢机理尚不完全清楚。基于此,本研究建立了TCS暴露的肝癌肿瘤细胞球模型,利用质谱成像技术分析对照组和暴露组间脂质小分子在肿瘤细胞球内丰度和分布的差异。结果表明,6μmol/L TCS暴露可以显著促进肝癌肿瘤细胞球的增长,并引起脂质代谢的变化。27种脂质代谢小分子(含19种甘油磷脂、3种甘油酯和5种鞘脂)的丰度在对照组和暴露组的肿瘤细胞球内发生了显著性的变化。在暴露组的19种甘油磷脂中,16种在肿瘤细胞球外围增殖区发生了显著性上调;在3种甘油酯中,1种在外围增殖区发生了显著性上调,2种在内部凋亡区发生了显著性下调;5种鞘脂在肿瘤细胞球内部凋亡区均发生了显著性下调。可见,TCS可能是通过促进肿瘤细胞球外围细胞的增殖以及抑制内层细胞的凋亡来促进三维肿瘤细胞球的增长。该结果可为进一步探讨环境污染物对肿瘤发展影响的分子机制提供参考。Triclosan(TCS),an antimicrobial additive,has been widely used in many daily consumer products.Although it is banned from using in soap products in 2016 by the USA Food and Drug Administration,it still can be used in many other products such as cosmetics,toys,mouthwash and toothpaste.Because of its ubiquitous characteristics,there is a growing concern over the impact of TCS on human health.Previous studies have reported that exposure to TCS could promote the development of hepatocellular carcinoma.However,little is known about the related mechanisms at the metabolic levels.In cancer research,multicellular tumor spheroids(MCTSs)are sphere-shaped cellular colonies,and which are considered to be the most appropriate in vitro cell model to test toxicities of chemicals because of their ability to mimic the main characteristics of solid tumors.To the best of our knowledge,no studies have tested the effect of TCS on the development of liver MCTS.Hence,in this work,liver MCTSs were exposed to TCS,and mass spectrometry imaging(MSI)was used to explore the variations of abundance and distribution of lipids in MCTS between exposure and control groups.The results revealed that treatment of 6μmol/L TCS could significantly promote the growth of liver MCTS and induce the lipid disorders in MCTS.Segmentation analysis of MCTS showed that there were three microregions including the outer proliferative area,the middle quiescent area and the inner necrotic area in MCTS.Further MSI data revealed that the abundance of 27 lipids including 19 glycerophospholipids(GPs),3 glycerolipids(GLs)and 5 sphingolipids(SPs)significantly changed in MCTS between treated and untreated groups.In GPs,a total of 16 up-regulated lipids located in the outer proliferative area of MCTS.In GLs,two up-regulated lipids located in the outer proliferative area,while one down-regulated lipid distributed in the inner area.In SPs,all five lipids with decreased levels located in the inner area.All these data suggested that the enhanced growth of liver MCTS induced by

关 键 词：质谱成像(MSI) 肿瘤细胞球 三氯生(TCS) 脂质代谢 细胞增殖 

分 类 号：O657.63[理学—分析化学]