靶向FOXM1信号通路诱导皮肤T细胞淋巴瘤细胞凋亡的体外评价。

IF 4.6
Shilpa Kuttikrishnan , Tariq Masoodi , Fareed Ahmad , Gulab Sher , Kirti S. Prabhu , Jericha M. Mateo , Joerg Buddenkotte , Tamam El-Elimat , Nicholas H. Oberlies , Cedric J. Pearce , Ajaz A. Bhat , Feras Q. Alali , Martin Steinhoff , Shahab Uddin
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引用次数: 0

摘要

背景:皮肤T细胞淋巴瘤(CTCL)是一种主要影响皮肤的T细胞衍生的非霍奇金淋巴瘤,其治疗具有重大挑战性和低生存率。目的:在本研究中,我们研究了真菌衍生的次级代谢产物新毛霉素B(NSP-B)对CTCL细胞系H9和HH的抗癌潜力。方法:使用细胞计数Kit-8(CCK8)测定细胞活力。膜联蛋白V/PI双染色法检测细胞凋亡。进行免疫印迹以检测蛋白质的表达。应用生物系统公司的高分辨率人类转录组阵列2.0用于检测基因表达。结果:NSP-B通过激活线粒体信号通路和胱天蛋白酶诱导CTCL细胞凋亡。我们观察到,在NSP-B处理的细胞中,BUB1B、Aurora激酶A和B、细胞周期蛋白依赖性激酶(CDKs)4和6以及polo-like激酶1(PLK1)的表达下调,Western印迹分析进一步证实了这一点。值得注意的是,在CTCL患者队列中,这些基因的高表达水平显示出总体生存率和无进展生存率降低。FOXM1和BUB1B的表达在NSP-B处理的CTCL细胞中表现出剂量依赖性降低。FOXM1沉默通过BUB1B下调降低细胞活力并增加细胞凋亡。此外,NSP-B抑制FOXM1调节的基因,如极光激酶A和B、CDKs 4和6以及PLK1。与单独治疗相比,硼替佐米和NSP-B的联合治疗在降低CTCL细胞活力和促进细胞凋亡方面显示出更大的疗效。结论:我们的研究结果表明,靶向FOXM1通路可能为CTCL管理提供一种有前景的治疗策略,NSP-B作为一种新的治疗选择具有重要的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
In vitro evaluation of Neosetophomone B inducing apoptosis in cutaneous T cell lymphoma by targeting the FOXM1 signaling pathway

Background

Cutaneous T cell lymphoma (CTCL) is a T cell-derived non-Hodgkin lymphoma primarily affecting the skin, with treatment posing a significant challenge and low survival rates.

Objective

In this study, we investigated the anti-cancer potential of Neosetophomone B (NSP-B), a fungal-derived secondary metabolite, on CTCL cell lines H9 and HH.

Methods

Cell viability was measured using Cell counting Kit-8 (CCK8) assays. Apoptosis was measured by annexin V/PI dual staining. Immunoblotting was performed to examine the expression of proteins. Applied Biosystems' high-resolution Human Transcriptome Array 2.0 was used to examine gene expression.

Results

NSP-B induced apoptosis in CTCL cells by activating mitochondrial signaling pathways and caspases. We observed downregulated expression of BUB1B, Aurora Kinases A and B, cyclin-dependent kinases (CDKs) 4 and 6, and polo-like kinase 1 (PLK1) in NSP-B treated cells, which was further corroborated by Western blot analysis. Notably, higher expression levels of these genes showed reduced overall and progression-free survival in the CTCL patient cohort. FOXM1 and BUB1B expression exhibited a dose-dependent reduction in NSP-B-treated CTCL cells.FOXM1 silencing decreased cell viability and increased apoptosis via BUB1B downregulation. Moreover, NSP-B suppressed FOXM1-regulated genes, such as Aurora Kinases A and B, CDKs 4 and 6, and PLK1. The combined treatment of Bortezomib and NSP-B showed greater efficacy in reducing CTCL cell viability and promoting apoptosis compared to either treatment alone.

Conclusion

Our findings suggest that targeting the FOXM1 pathway may provide a promising therapeutic strategy for CTCL management, with NSP-B offering significant potential as a novel treatment option.

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