金属蛋白酶(MMPs)在血液恶性肿瘤中的作用,如急性髓细胞性白血病(AML),骨髓增生异常肿瘤(MDS),多发性骨髓瘤(MM),有据可查,尽管治疗取得了进展,但这些病理结果仍然较差。在这项研究中,我们研究了batimastat(BB-94)的作用,MMP抑制剂(MMPi),在AML的单次给药和每日给药方案中,MDS,和MM细胞系。我们使用四种血液肿瘤细胞系:HL-60和NB-4细胞作为AML模型,F36-P细胞作为MDS模型,和H929细胞作为MM的模型。我们还测试了batimastat在正常人淋巴细胞系(IMC细胞)中的毒性。BB-94在剂量下降低细胞活力和密度-,time-,行政计划-,和细胞系依赖的方式,AML细胞显示较高的反应。诱导细胞凋亡和细胞周期停滞的功效取决于细胞系(在AML细胞中具有较高的作用),尤其是在每日剂量较低的情况下,这可以减轻治疗毒性。此外,BB-94通过胱天蛋白酶和ERK1/2途径激活细胞凋亡。这些发现强调了batimastat在血液恶性肿瘤中的治疗潜力,每日给药作为一种最小化不良反应的策略。
The role of metalloproteinases (MMPs) in hematological malignancies, like acute myeloid leukemia (AML), myelodysplastic neoplasms (MDS), and multiple myeloma (MM), is well-documented, and these pathologies remain with poor outcomes despite treatment advancements. In this study, we investigated the effects of batimastat (BB-94), an MMP inhibitor (MMPi), in single-administration and daily administration schemes in AML, MDS, and MM cell lines. We used four hematologic neoplasia cell lines: the HL-60 and NB-4 cells as AML models, the F36-P cells as an MDS model, and the H929 cells as a model of MM. We also tested batimastat toxicity in a normal human lymphocyte cell line (IMC cells). BB-94 decreases cell viability and density in a dose-, time-, administration-scheme-, and cell-line-dependent manner, with the AML cells displaying higher responses. The efficacy in inducing apoptosis and cell cycle arrests is dependent on the cell line (higher effects in AML cells), especially with lower daily doses, which may mitigate treatment toxicity. Furthermore, BB-94 activated apoptosis via caspases and ERK1/2 pathways. These findings highlight batimastat\'s therapeutic potential in hematological malignancies, with daily dosing emerging as a strategy to minimize adverse effects.