Multimode MALDI-MSI deciphers matrine-induced metabolic reprogramming in prostate cancer xenografts: spatial mapping of low-molecular-weight compound alterations

作者：Jia Xu, Qin Liang, Xiao Liang, Lulu Chen, Juexin Wang, Hua Guo, Fengmei Wang, Rong Wu, Xiaojing An, Wenjuan Liu, Xiaodong Wang, Qi Li · 发表于：Frontiers in Pharmacology · 年份：2025 · DOI：10.3389/fphar.2025.1627864 · 被引用次数：3 · 研究领域：Bioactive natural compounds、Metabolomics and Mass Spectrometry Studies、Sirtuins and Resveratrol in Medicine

Background: Matrine, a bioactive isoquinoline alkaloid, exhibits antitumor efficacy by modulating multiple signaling pathways to suppress cancer cell proliferation, migration and invasion. However, its metabolic regulatory mechanisms in prostate cancer intervention require systematic characterization. Methods: We implemented matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) for spatial metabolomic profiling of prostate tissues, integrated with multivariate analytical approaches including principal component analysis, Pearson correlation-based clustering heatmap, partial least squares-discriminant analysis, and hierarchical clustering heatmap analysis. This multimodal strategy enabled comparative evaluation of low-molecular-weight metabolite distributions across normal control, prostate cancer, and matrine-treated prostate cancer cohorts. Results: Multi-omics integration identified 19 discriminant metabolites (VIP >1.0) spanning lipid signaling mediators (choline, glycerophosphoglycerol, sphinganine, glycerophosphoinositol, linoleic acid, oleic acid, N,N-Dimethylsphingosine), amino acid network regulators (cysteic acid, 5-Hydroxylysine, glutamine-glutamate axis components), nucleotide biosynthesis (adenine, Ribose 1,5-bisphosphate, uracil, dihydrouracil, deoxyinosine, adenosine), markers of oxidative damage (8-Hydroxyguanine) and cofactor of nitric oxide synthases and aromatic amino acid hydroxylases (tetrahydropteridine). Linoleic acid, oleic a...