Breast cancer is the most common cancer in women, the so-called “Triple-Negative Breast Cancer” (TNBC) subtype remaining the most challenging to treat, with low tumor-free survival and poor clinical evolution. Therefore, there is a clear medical need for innovative and more efficient treatment options for TNBC. The aim of the present study was to evaluate the potential therapeutic interest of the association of the tumor-penetrating BR2 peptide with monophosphoester 2-aminoethyl dihydrogen phosphate (2-AEH2P), a monophosphoester involved in cell membrane turnover, in TNBC. For that purpose, viability, migration, proliferative capacity, and gene expression analysis of proteins involved in the control of proliferation and apoptosis were evaluated upon treatment of an array of TNBC cells with the BR2 peptide and 2-AEH2P, either separately or combined. Our data showed that, while possessing limited single-agent activity, the 2-AEH2P+BR2 association promoted significant cytotoxicity in TNBC cells but not in normal cells, with reduced proliferative potential and inhibition of cell migration. Mechanically, the 2-AEH2P+BR2 combination promoted an increase in cells expressing p53 caspase 3 and caspase 8, a reduction in cells expressing tumor progression and metastasis markers such as VEGF and PCNA, as well as a reduction in mitochondrial electrical potential. Our results indicate that the combination of the BR2 peptide with 2-AEH2P+BR2 may represent a promising therapeutic strategy in TNBC with potential use in clinical settings.
乳腺癌是女性最常见的恶性肿瘤，其中被称为“三阴性乳腺癌”（TNBC）的亚型治疗最为棘手，患者无瘤生存率低且临床预后较差。因此，针对TNBC开发创新且更有效的治疗方案具有明确的临床需求。本研究旨在评估肿瘤穿透肽BR2与单磷酸酯2-氨基乙基二氢磷酸酯（2-AEH2P，一种参与细胞膜更新的单磷酸酯）联合应用对TNBC的潜在治疗价值。为此，我们通过单独或联合使用BR2肽和2-AEH2P处理一系列TNBC细胞系，系统评估了细胞活力、迁移能力、增殖潜能，以及与增殖和凋亡调控相关蛋白的基因表达变化。实验数据显示，虽然单一药物活性有限，但2-AEH2P与BR2的联合应用能显著诱导TNBC细胞（而非正常细胞）的细胞毒性，同时降低细胞增殖潜能并抑制细胞迁移。机制研究表明，2-AEH2P+BR2联合治疗能促进p53、caspase 3和caspase 8的表达，降低血管内皮生长因子（VEGF）和增殖细胞核抗原（PCNA）等肿瘤进展与转移标志物的表达水平，并引起线粒体膜电位下降。这些结果表明，BR2肽与2-AEH2P的联合应用可能成为TNBC领域具有临床转化潜力的新型治疗策略。
肿瘤(癌症)患者之家