肿瘤细胞治疗研究
英文原题：Agrimol B induces apoptosis and ferroptosis in acute monocytic leukemia by targeting EGFR/ERK1/2 signaling and activating SIRT1.
这些发现表明，Agrimol B通过多种机制发挥强效抗白血病活性，突显其作为AMoL治疗候选药物的潜力。
白血病是一种侵袭性血液系统恶性肿瘤，全球发病率和死亡率均较高。尽管CAR-T细胞疗法和靶向治疗取得了进展，但急性髓系白血病和高危复发患者由于异质性和耐药性，仍面临严峻的治疗挑战。Agrimol B（AB）是一种从食药两用植物龙芽草（Agrimonia pilosa Ledeb.）中分离得到的生物活性天然化合物，已显示出显著的抗癌潜力。然而，其在白血病中的作用尚未被研究。在此，我们证明AB在急性单核细胞白血病（AMoL）小鼠模型中显著减轻白血病负荷，并在体外抑制THP-1细胞的增殖、侵袭和迁移。在机制上，AB与EGFR相互作用并抑制ERK1/2信号通路，从而激活FOXO1。此外，AB上调SIRT1表达并促进FOXO1去乙酰化，导致HMOX1激活，进而触发铁死亡。这些发现表明，Agrimol B通过多种机制发挥强效抗白血病活性，凸显其作为AMoL治疗候选药物的潜力。
Leukemia is an aggressive hematologic malignancy with high global morbidity and mortality. Despite advances in CAR-T cell therapy and targeted treatments, acute myeloid leukemia and high-risk relapsed cases continue to face formidable therapeutic challenges owing to heterogeneity and drug resistance. Agrimol B (AB), a bioactive natural compound isolated from the edible and medicinal plant Agrimonia pilosa Ledeb., has demonstrated notable anticancer potential. However, its role in leukemia has not yet been investigated. Here, we demonstrate that AB significantly reduces leukemia burden in an Acute Monocytic Leukemia (AMoL) mouse model and suppresses proliferation, invasion, and migration of THP-1 cells in vitro. Mechanistically, AB interacts with EGFR and inhibits ERK1/2 signaling, thereby activating FOXO1. In addition, AB upregulates SIRT1 expression and promotes FOXO1 deacetylation, leading to HMOX1 activation and subsequently triggers ferroptosis. These findings indicate that Agrimol B exerts potent anti-leukemic activity through multiple mechanisms, highlighting its potential as a therapeutic candidate for AMoL.
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