Department of Neurosurgery, Medical Faculty, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle (Saale), Germany.
Int J Mol Sci. 2024 Sep 27;25(19):10389. doi: 10.3390/ijms251910389.
The chemotherapeutic agent vincristine is commonly used for a variety of hematologic cancers, as well as solid tumors of the head and neck, bronchial carcinoma, as part of the procarbazine, lomustine and vincristine (PCV) regimen, for glioma. Damage to nerve tissue (neuropathy) is often dose-limiting and restricts treatment. Nimodipine is a calcium antagonist that has also shown neuroprotective properties in preliminary studies. In this approach here, we investigated the effects of the combination of vincristine and nimodipine on three cancer cell lines (A549, SAS and LN229) and neuronal cells (RN33B, SW10). Fluorescence microscopy, lactate dehydrogenase (LDH) assays and Western blot analyses were used. Nimodipine was able to enhance the cell death effects of vincristine in all tumor cells, while neuronal cells were protected and showed less cell death. There was an opposite change in the protein levels of Ak strain transforming/protein kinase B (AKT) in tumor cells (down) and neuronal cells (up), with simultaneous increased protein levels of cyclic adenosine monophosphate response element-binding protein (CREB) in all cell lines. In the future, this approach may improve tumor response to chemotherapy and reduce unwanted side effects such as neuropathy.
长春新碱是一种常用的化疗药物，可用于多种血液系统癌症以及头颈部、支气管癌和神经胶质瘤等实体瘤。长春新碱作为丙卡巴肼、洛莫司汀和长春新碱（PCV）方案的一部分，与其他药物联合用于治疗神经母细胞瘤。长春新碱会造成神经组织损伤（神经病变），这通常是剂量限制因素，会限制治疗效果。尼莫地平是一种钙通道拮抗剂，在初步研究中已显示出神经保护作用。在此项研究中，我们研究了长春新碱和尼莫地平联合使用对三种癌细胞系（A549、SAS 和 LN229）和神经元细胞（RN33B、SW10）的影响。使用荧光显微镜、乳酸脱氢酶（LDH）检测和 Western blot 分析。尼莫地平能够增强长春新碱对所有肿瘤细胞的细胞死亡作用，而神经元细胞受到保护，细胞死亡减少。肿瘤细胞中 AK 株转化/蛋白激酶 B（AKT）的蛋白水平发生相反变化（下调），神经元细胞的蛋白水平则上升（上调），同时所有细胞系中环磷酸腺苷反应元件结合蛋白（CREB）的蛋白水平也升高。将来，这种方法可能会提高肿瘤对化疗的反应，减少神经病变等不必要的副作用。
