PDZ结合激酶（PBK）被报道为恶性预后因子，并且是抗癌治疗的一个有前景的分子靶点。在这里，我们旨在研究特定PBK抑制剂OTS514对口腔鳞状细胞癌细胞生存的影响。我们使用四种口腔鳞状细胞癌细胞系（HSC-2，HSC-3，SAS和OSC-19）来检查OTS514对细胞生存和凋亡的影响。进行了DNA微阵列分析以研究OTS514对口腔鳞状细胞癌细胞基因表达的影响。进行基因集富集分析以确定与OTS514抗增殖效应相关的分子特征。OTS514对口腔鳞状细胞癌细胞的细胞生存呈剂量依赖性下降，OTS514的给药能够抑制免疫缺陷小鼠中HSC-2来源的肿瘤生长。OTS514处理显著增加了凋亡细胞数和caspase-3 / 7活性。重要的是，OTS514抑制E2F靶基因的表达，引起转录因子E2F1蛋白水平显著下降。此外，TP53敲除削弱了OTS514诱导凋亡作用。OTS514通过降低E2F靶基因的表达抑制口腔鳞状细胞癌细胞的增殖，并通过介导p53信号通路诱导凋亡。这些结果突出了PBK抑制剂在开发分子靶向治疗口腔鳞状细胞癌方面的临床应用价值。本文受版权保护。版权所有。

PDZ-binding kinase (PBK) has been reported as a poor prognostic factor and is a promising molecular target for anti-cancer therapeutics. Here, we aimed to investigate the effect of specific PBK inhibitor OTS514 on the survival of OSCC cells.Four OSCC cell lines (HSC-2, HSC-3, SAS, and OSC-19) were used to examine the effect of OTS514 on cell survival and apoptosis. DNA microarray analysis was conducted to investigate the effect of OTS514 on gene expression in OSCC cells. Gene Set Enrichment Analysis was performed to identify molecular signatures related to the anti-proliferative effect of OTS514.OTS514 decreased the cell survival of OSCC cells dose-dependently, and administration of OTS514 readily suppressed the HSC-2-derived tumor growth in immunodeficient mice. Treatment with OTS514 significantly increased the number of apoptotic cells and Caspase-3/7 activity. Importantly, OTS514 suppressed the expression of E2F target genes with a marked decrease in protein levels of E2F1, a transcriptional factor. Moreover, TP53 knockdown attenuated OTS514-induced apoptosis.OTS514 suppressed the proliferation of OSCC cells by downregulating the expression of E2F target genes and induced apoptosis by mediating the p53 signaling pathway. These results highlight the clinical application of PBK inhibitors in the development of molecular-targeted therapeutics against OSCC.This article is protected by copyright. All rights reserved.