伊曲康唑调节肿瘤相关巨噬细胞中的磷脂水平。
Itraconazole Modulates Phospholipid Levels in Tumor-associated Macrophages.
机构信息
Department of Obstetrics and Gynecology, School of Medicine, Hyogo Medical University, Nishinomiya, Japan.
Department of Obstetrics and Gynecology, School of Medicine, Hyogo Medical University, Nishinomiya, Japan;
出版信息
Anticancer Res. 2023 May;43(5):1981-1984. doi: 10.21873/anticanres.16358.
BACKGROUND/AIM: Itraconazole, an antifungal drug, repolarizes pro-tumorigenic M2 tumor-associated macrophages to anti-tumorigenic M1-like phenotypes, thereby inhibiting the proliferation of cancer cells; however, the underlying mechanism remains unclear. Therefore, we investigated the effect of itraconazole on membrane-associated lipids in tumor-associated macrophages (TAM).
MATERIALS AND METHODS
M1 and M2 macrophages were derived from the human monocyte leukemia cell line (THP-1) and cultured with or without 10 μM itraconazole. Cells were homogenized and subjected to liquid chromatography/mass spectrometry (LC/MS) analysis to estimate the glycerophospholipid levels in the cells.
RESULTS
Lipidomic analysis results, displayed on a volcano plot, revealed that itraconazole-induced altered phospholipid composition, with more pronounced changes in M2 macrophages than in M1. Notably, itraconazole significantly increased intracellular phosphatidylinositol and lysophosphatidylcholine levels in M2 macrophages.
CONCLUSION
Itraconazole modulates the lipid metabolism of TAMs, which could have implications for the development of novel cancer therapies.
背景/目的：伊曲康唑是一种抗真菌药物，可将促肿瘤的 M2 肿瘤相关巨噬细胞（TAM）重极化为抗肿瘤的 M1 样表型，从而抑制癌细胞的增殖；然而，其潜在机制尚不清楚。因此，我们研究了伊曲康唑对 TAM 细胞膜相关脂质的影响。
材料与方法
M1 和 M2 巨噬细胞来源于人单核白血病细胞系（THP-1），并在有或没有 10 μM 伊曲康唑的情况下进行培养。将细胞匀浆并进行液相色谱/质谱（LC/MS）分析，以估计细胞中甘油磷脂的水平。
结果
脂质组学分析结果以火山图显示，伊曲康唑诱导的磷脂组成改变，M2 巨噬细胞中的变化比 M1 更明显。值得注意的是，伊曲康唑显著增加了 M2 巨噬细胞内的磷脂酰肌醇和溶血磷脂酰胆碱水平。
结论
伊曲康唑调节 TAM 的脂质代谢，这可能对开发新型癌症治疗方法具有重要意义。
Zotero 插件