Ezzat Abeer, Shafiek Mohga, Shawki Shimaa, Abdel-Ghany Shaimaa, Nazih Mahmoud, Sabit Hussein
Department of Medical Biotechnology, College of Biotechnology, Misr University for Science and Technology, P. O. Box 77, Giza, Egypt.
Department of Chemistry, Faculty of Science, Helwan University, Cairo, 11795, Egypt.
Sci Rep. 2025 Jan 13;15(1):1824. doi: 10.1038/s41598-024-84744-y.
This study was designed to assess the effect of brentuximab vedotin on several breast cancer cell lines in terms of promoting apoptosis and managing cancer progression. Additionally, the study investigated the potential of repurposing this drug for new therapeutic reasons, beyond its original indications. The study evaluates the cytotoxic effects of Brentuximab vedotin across five cell lines: normal human skin fibroblasts (HSF), three breast cancer cell lines (MCF-7, MDA-MB-231, and T-47D), and histiocytic lymphoma (U-937). Brentuximab treatment was administered at four time points (0, 24, 48, and 72 h), with cell viability assessed at each interval. HSF cells, serving as controls, exhibited minimal viability loss (above 70%), indicating limited toxicity in normal fibroblasts. In contrast, MCF-7 and MDA-MB-231 cells demonstrated time-dependent reductions in viability, with a pronounced decline by 72 h, suggesting Brentuximab's efficacy in both ER-positive and triple-negative breast cancer. T-47D cells also showed decreased viability, though at a slower rate. U-937 cells exhibited the most substantial reduction, highlighting Brentuximab's potent activity against hematologic malignancies. Wound healing assays further revealed that Brentuximab significantly impaired the migration and healing capacity of cancer cells compared to untreated controls. Additionally, cell cycle analysis indicated G2/M phase arrest in cancer cells, particularly in MCF-7 and MDA-MB-231, while HSF cells remained largely unaffected. Apoptosis detection confirmed Brentuximab-induced cell death, with significant increases in late apoptosis in cancer lines, especially by 72 h. Gene expression analysis revealed upregulation of pro-apoptotic genes (BAX, Caspase 3, and Caspase 9) in cancer cells, alongside a decrease in anti-apoptotic BCL-2 expression. These findings suggest Brentuximab's selective cytotoxicity against cancer cells and its potential as an effective therapeutic agent, particularly in breast cancer and histiocytic lymphoma.
本研究旨在评估维布妥昔单抗对几种乳腺癌细胞系在促进细胞凋亡和控制癌症进展方面的作用。此外，该研究还调查了将这种药物用于超出其原始适应症的新治疗用途的潜力。该研究评估了维布妥昔单抗对五种细胞系的细胞毒性作用：正常人皮肤成纤维细胞（HSF）、三种乳腺癌细胞系（MCF-7、MDA-MB-231和T-47D）以及组织细胞淋巴瘤（U-937）。在四个时间点（0、24、48和72小时）给予维布妥昔单抗治疗，并在每个时间间隔评估细胞活力。作为对照的HSF细胞显示出最小的活力损失（高于70%），表明对正常成纤维细胞的毒性有限。相比之下，MCF-7和MDA-MB-231细胞的活力呈现出时间依赖性下降，到72小时时显著下降，这表明维布妥昔单抗对雌激素受体阳性和三阴性乳腺癌均有效。T-47D细胞的活力也有所下降，不过速度较慢。U-937细胞的活力下降最为显著，突出了维布妥昔单抗对血液系统恶性肿瘤的强大活性。伤口愈合试验进一步表明，与未处理的对照相比，维布妥昔单抗显著损害了癌细胞的迁移和愈合能力。此外，细胞周期分析表明癌细胞出现G2/M期阻滞，特别是在MCF-7和MDA-MB-231细胞中，而HSF细胞基本未受影响。凋亡检测证实了维布妥昔单抗诱导的细胞死亡，癌症细胞系中晚期凋亡显著增加，尤其是在72小时时。基因表达分析显示癌细胞中促凋亡基因（BAX、半胱天冬酶3和半胱天冬酶9）上调，同时抗凋亡的BCL-2表达下降。这些发现表明维布妥昔单抗对癌细胞具有选择性细胞毒性及其作为有效治疗剂的潜力，特别是在乳腺癌和组织细胞淋巴瘤方面。
