Zinc finger protein 275 (ZNF275) is a C2H2-type transcription factor that is localized on chromosome Xq28. Whether ZNF275 participates in modulating the biological behaviors of cervical cancer has not been determined to our knowledge. The present study employed CCK-8, BrdU, flow cytometry, and a transwell assay to investigate the cell viability, proliferation, apoptosis, migration, and invasion of cervical cancer cells. The application of Western blotting and immunohistochemistry (IHC) aims to assess ZNF275 protein expression and identify the signaling pathway relevant to ZNF275-mediated effects on cervical cancer. The therapeutic impact of the combined therapy of the AKT inhibitor triciribine and cisplatin was evaluated on cervical cancer patient-derived xenograft (PDX) models expressing high ZNF275. The current research illustrated that cervical cancer tissue exhibited a higher expression of ZNF275 in contrast to the surrounding normal cervical tissue. The downregulation of ZNF275 suppressed cell viability, migration, and invasion, and facilitated the apoptosis of SiHa and HeLa cells via weakening AKT/Bcl-2 signaling pathway. Moreover, triciribine synergized with cisplatin to reduce cell proliferation, migration, and invasion, and enhanced the apoptosis of SiHa cells expressing high ZNF275. In addition, the combination treatment of triciribine and cisplatin was more effective in inducing tumor regression than single agents in cervical cancer PDX models expressing high ZNF275. Collectively, the current findings demonstrated that ZNF275 serves as a sufficiently predictive indicator of the therapeutic effectiveness of the combined treatment of triciribine and cisplatin on cervical cancer. Combining triciribine with cisplatin greatly broadens the therapeutic options for cervical cancer expressing high ZNF275, but further research is needed to confirm these results.
锌指蛋白275（ZNF275）是一种定位于Xq28染色体的C2H2型转录因子。目前尚未明确ZNF275是否参与调控宫颈癌的生物学行为。本研究采用CCK-8、BrdU、流式细胞术及Transwell实验，系统检测了ZNF275对宫颈癌细胞活力、增殖、凋亡、迁移及侵袭能力的影响。通过蛋白质印迹法和免疫组织化学技术，评估ZNF275蛋白表达水平，并探究其介导宫颈癌生物学效应的相关信号通路。在表达高水平ZNF275的宫颈癌患者来源异种移植（PDX）模型中，评估了AKT抑制剂曲西立滨与顺铂联合疗法的治疗效果。研究结果显示：与癌旁正常组织相比，宫颈癌组织中ZNF275表达显著升高。下调ZNF275可通过抑制AKT/Bcl-2信号通路，有效抑制SiHa和HeLa细胞的活力、迁移及侵袭能力，并促进细胞凋亡。值得注意的是，曲西立滨与顺铂联用能协同抑制高表达ZNF275的SiHa细胞增殖、迁移和侵袭，并增强其凋亡。在表达高水平ZNF275的宫颈癌PDX模型中，联合用药比单药治疗更能有效诱导肿瘤消退。综上所述，本研究表明ZNF275可作为预测曲西立滨与顺铂联合治疗宫颈癌疗效的有效指标。该联合治疗方案为高表达ZNF275的宫颈癌患者提供了新的治疗选择，但其临床应用价值仍需进一步研究验证。
肿瘤(癌症)患者之家