Evans Blue Acts as a Selective Inhibitor of CaMKII-α to Impede the Progression of TCL Identified by HTS

IF 4.5 2区 医学 Q1 ONCOLOGY
Cancer Science Pub Date : 2025-04-04 DOI:10.1111/cas.70051
Jianru Tian, Aiqin Zhang, Lansong Li, Hong Liu, Hui Jiang, Ruqi Liang
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引用次数: 0

Abstract

T-cell lymphoma (TCL) poses a significant challenge in clinical oncology, characterized by its aggressive behavior and resistance to conventional therapies. Despite considerable research efforts, the prognosis for TCL patients remains poor, primarily due to the lack of effective therapeutic strategies that can inhibit tumor progression and metastasis. In this study, we identified CaMKII-α as a potential therapeutic target for TCL. To explore its role in TCL pathogenesis, we investigated its effects on TCL cell lines. Protein expression levels within the PI3K-AKT signaling pathway were assessed using western blot analysis. Through siRNA-mediated gene silencing, we downregulated CaMKII-α expression and monitored TCL cell proliferation. Furthermore, we identified Evans Blue (IC50 = 197.1 nM) as a selective small-molecule inhibitor of CaMKII-α through high-throughput screening (HTS). Evans Blue demonstrated significant tumor-suppressive effects, potentially inhibiting TCL cell proliferation via regulation of the PI3K-AKT signaling pathway. Notably, the antitumor effect of Evans Blue was comparable to that observed with genetic CaMKII-α ablation, highlighting its potential as a novel therapeutic strategy for the treatment of TCL.

Abstract Image

Evans Blue作为CaMKII-α的选择性抑制剂,通过HTS鉴定可阻止TCL的进展。
T细胞淋巴瘤(TCL)以其侵袭性和对传统疗法的抗药性为特征,给临床肿瘤学带来了巨大挑战。尽管开展了大量研究工作,TCL 患者的预后仍然很差,这主要是由于缺乏能抑制肿瘤进展和转移的有效治疗策略。在本研究中,我们发现 CaMKII-α 是 TCL 的潜在治疗靶点。为了探索它在 TCL 发病机制中的作用,我们研究了它对 TCL 细胞系的影响。我们使用 Western 印迹分析评估了 PI3K-AKT 信号通路中的蛋白表达水平。通过 siRNA 介导的基因沉默,我们下调了 CaMKII-α 的表达,并监测了 TCL 细胞的增殖。此外,我们还通过高通量筛选(HTS)确定了伊文思蓝(IC50 = 197.1 nM)作为 CaMKII-α 的选择性小分子抑制剂。伊文思蓝具有明显的肿瘤抑制作用,可能通过调节 PI3K-AKT 信号通路抑制 TCL 细胞增殖。值得注意的是,伊文思蓝的抗肿瘤效果与基因CaMKII-α消融所观察到的效果相当,这凸显了它作为一种治疗TCL的新型治疗策略的潜力。
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来源期刊
Cancer Science
Cancer Science 医学-肿瘤学
自引率
3.50%
发文量
406
审稿时长
2 months
期刊介绍: Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.
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