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

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 (IC = 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.