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苯乙基异硫氰酸酯调节巨噬细胞迁移抑制因子并抑制胶质母细胞瘤细胞的恶性表型。

Phenethyl isothiocyanate modulates macrophage migration inhibitory factor and suppresses malignant phenotypes of glioblastoma cells.

作者信息

Lin Jeng-Rong, Liao Wen-Chieh, Chu Yin-Hung, Chou Yu-Cheng, Liu Chiung-Hui

机构信息

Doctoral Program in Tissue Engineering and Regenerative Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.

Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.

出版信息

Food Funct. 2025 Jul 1;16(13):5573-5585. doi: 10.1039/d5fo00415b.

DOI:10.1039/d5fo00415b
PMID:40528798
Abstract

Phenethyl Isothiocyanate (PEITC) is a well-studied compound within the isothiocyanate family. Accumulating evidence indicates that PEITC induces apoptosis and inhibits the growth of various cancer cells , including aggressive glioblastoma cells. However, its tumor suppression effects and mechanisms remain largely unexplored. In this study, we utilized cell culture experiments and an orthotopic transplant brain tumor model in mice to evaluate the impact of PEITC on tumor growth, physiological changes, and immune cell populations. Our results showed that PEITC significantly reduced the viability of glioma cells while having moderate effects on astrocytes. , PEITC effectively inhibited cell viability, migration, and invasion in GL-261 cells. , PEITC treatment led to prolonged survival rates and reduced tumor volumes in mice without significant toxicity. Notably, PEITC increased the populations of natural killer (NK) cells and natural killer T (NKT) cells in peripheral blood, indicating an immunomodulatory effect. Migration Inhibitory Factor (MIF) was identified as a potential direct target of PEITC. Our findings revealed that PEITC significantly reduced MIF expression in GL-261 cells, both in culture and in orthotopic tumor tissue, and decreased MIF-induced cellular signaling. These results suggest that PEITC has potential to be a therapeutic agent for glioblastoma by inhibiting tumor growth and modulating the immune response through MIF suppression.

摘要

苯乙基异硫氰酸酯(PEITC)是异硫氰酸酯家族中一种经过充分研究的化合物。越来越多的证据表明,PEITC可诱导细胞凋亡并抑制包括侵袭性胶质母细胞瘤细胞在内的多种癌细胞的生长。然而,其肿瘤抑制作用和机制在很大程度上仍未被探索。在本研究中,我们利用细胞培养实验和小鼠原位移植脑肿瘤模型来评估PEITC对肿瘤生长、生理变化和免疫细胞群体的影响。我们的结果表明,PEITC显著降低了胶质瘤细胞的活力,而对星形胶质细胞有中度影响。此外,PEITC有效抑制了GL - 261细胞的活力、迁移和侵袭。而且,PEITC治疗可提高小鼠的生存率并减小肿瘤体积,且无明显毒性。值得注意的是,PEITC增加了外周血中自然杀伤(NK)细胞和自然杀伤T(NKT)细胞的数量,表明其具有免疫调节作用。迁移抑制因子(MIF)被确定为PEITC的潜在直接靶点。我们的研究结果显示,PEITC在培养物和原位肿瘤组织中均显著降低了GL - 261细胞中MIF的表达,并减少了MIF诱导的细胞信号传导。这些结果表明,PEITC有潜力通过抑制肿瘤生长和通过抑制MIF调节免疫反应,成为胶质母细胞瘤的治疗药物。

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