随着发病率的迅速上升，乳头状甲状腺癌（PTC）已成为最常见的头颈部癌症。中药材独活素可抑制各种癌细胞（包括PTC细胞），但其对PTC细胞的脂质组成及脂质变化的作用尚未研究。本研究使用UHPLC/Q-TOF-MS平台对独活素处理的PTC细胞进行全面脂质组学分析，探讨了脂质组成及变化特定脂质物种之间的关联。通过网络药理学和分子对接的方法，展示了独活素、变化的脂质物种和潜在靶向基因之间的关联。结果显示，共鉴定出34种脂质类和1736种脂质物种。脂质类分析显示，与对照组相比，独活素处理的PTC细胞中脂肪酸（FA）、胆固醇酯（ChE）、简单的葡萄糖酰系列3（CerG3）和溶解磷脂酰甘油（LPG）的水平更高，但类固醇醇（ZyE）和单半乳糖基二酰基甘油（MGDG）的水平更低，但差异不显著。独活素处理的PTC细胞中，一些特定的脂质物种发生了显著变化，如磷脂酰胆碱（PC）（12:0e/16:0）、PC（18:0/20:4）、CerG3（d18:1/24:1）、溶解磷酰乙醇胺（LPE）（18:0）、磷脂酰肌醇（PI）（19:0/20:4）、溶解磷脂酰胆碱（LPC）（28:0）、ChE（22:6）增加，磷脂酰乙醇胺（PE）（16:1/17:0）、PC（34:1）和PC（16:0p/18:0）下降。网络药理学和脂质组学的联合分析发现了四个关键靶点（PLA2G4A、LCAT、LRAT和PLA2G2A），其中PLA2G2A和PLA2G4A能够与独活素结合，分子对接进一步印证了这个结果。结果表明，独活素处理的PTC细胞的脂质组成及特定脂质物种发生了显著变化。这些变化的脂质物种（如PC（34:1）和PC（16:0p/18:0））可能参与了独活素的抗肿瘤机制。PLA2G2A和PLA2G4A可能在独活素处理的PTC细胞中发挥关键作用。 © 2023. 作者（们）保留所有权利。

With fast rising incidence, papillary thyroid carcinoma (PTC) is the most common head and neck cancer. Parthenolide, isolated from traditional Chinese medicine, inhibits various cancer cells, including PTC cells. The aim was to investigate the lipid profile and lipid changes of PTC cells when treated with parthenolide.Comprehensive lipidomic analysis of parthenolide treated PTC cells was conducted using a UHPLC/Q-TOF-MS platform, and the changed lipid profile and specific altered lipid species were explored. Network pharmacology and molecular docking were performed to show the associations among parthenolide, changed lipid species, and potential target genes.With high stability and reproducibility, a total of 34 lipid classes and 1736 lipid species were identified. Lipid class analysis indicated that parthenolide treated PTC cells contained higher levels of fatty acid (FA), cholesterol ester (ChE), simple glc series 3 (CerG3) and lysophosphatidylglycerol (LPG), lower levels of zymosterol (ZyE) and Monogalactosyldiacylglycerol (MGDG) than controlled ones, but with no significant differences. Several specific lipid species were changed significantly in PTC cells treated by parthenolide, including the increasing of phosphatidylcholine (PC) (12:0e/16:0), PC (18:0/20:4), CerG3 (d18:1/24:1), lysophosphatidylethanolamine (LPE) (18:0), phosphatidylinositol (PI) (19:0/20:4), lysophosphatidylcholine (LPC) (28:0), ChE (22:6), and the decreasing of phosphatidylethanolamine (PE) (16:1/17:0), PC (34:1) and PC (16:0p/18:0). Four key targets (PLA2G4A, LCAT, LRAT, and PLA2G2A) were discovered when combining network pharmacology and lipidomics. Among them, PLA2G2A and PLA2G4A were able to bind with parthenolide confirmed by molecular docking.The changed lipid profile and several significantly altered lipid species of parthenolide treated PTC cells were observed. These altered lipid species, such as PC (34:1), and PC (16:0p/18:0), may be involved in the antitumor mechanisms of parthenolide. PLA2G2A and PLA2G4A may play key roles when parthenolide treated PTC cells.© 2023. The Author(s).