Abstract：
Mitotic inhibitors are drugs commonly used in chemotherapy, but their nonspecific and indiscriminate distribution throughout the body after intravenous administration can lead to serious side effects, particularly on the cardiovascular system. In this context, our investigation into the mechanism of the cytotoxic effects on endothelial cells of mitotic inhibitors widely used in cancer treatment, such as paclitaxel (also known as Taxol) and Vinca alkaloids, holds significant practical implications. Understanding these mechanisms can lead to more targeted and less harmful cancer treatments. Human aorta endothelial cells (HAECs) were incubated with selected mitotic inhibitors in a wide range of concentrations close to those in human plasma during anticancer therapy. The analysis of single cells imaged by Raman spectroscopy allowed for visualization of the nuclear, cytoplasmic, and perinuclear areas to assess biochemical changes induced by the drug\'s action. The results showed significant changes in the morphology and molecular composition of the nucleus. Moreover, an effect of a given drug on the cytoplasm was observed, which can be related to its mechanism of action (MoA). Raman data supported by fluorescence microscopy measurements identified unique changes in DNA form and proteins and revealed drug-induced inflammation of endothelial cells. The primary goal of mitotic inhibitors is based on the impairment of tubulin formation and the inhibition of the mitosis process. While all three drugs affect microtubules and disrupt cell division, they do so through different MoA, i.e., Vinca alkaloids inhibit microtubule formation, whereas paclitaxel stabilizes microtubules. To sum up, the work shows how a specific drug can interact with endothelial cells.
摘要：
有丝分裂抑制剂是化疗中常用的药物，但是静脉注射后它们在全身的非特异性和不分青红皂白的分布会导致严重的副作用，尤其是心血管系统。在这种情况下，我们研究了广泛用于癌症治疗的有丝分裂抑制剂对内皮细胞的细胞毒性作用机制，如紫杉醇（也称为紫杉醇）和长春花生物碱，具有重大的实际意义。了解这些机制可以导致更有针对性和更少有害的癌症治疗。在抗癌治疗期间，将人主动脉内皮细胞（HAEC）与选定的有丝分裂抑制剂以接近人血浆中的浓度范围孵育。通过拉曼光谱成像的单细胞分析允许核的可视化，细胞质，和核周区域，以评估药物作用引起的生化变化。结果表明，核的形态和分子组成发生了显着变化。此外，观察到给定药物对细胞质的影响，这可能与其作用机制(MoA)有关。荧光显微镜测量支持的拉曼数据鉴定了DNA形式和蛋白质的独特变化，并揭示了药物诱导的内皮细胞炎症。有丝分裂抑制剂的主要目标是基于微管蛋白形成的损害和有丝分裂过程的抑制。虽然这三种药物都会影响微管并破坏细胞分裂，他们通过不同的MoA这样做，即，长春花生物碱抑制微管形成，而紫杉醇稳定微管。总而言之,这项工作展示了特定药物如何与内皮细胞相互作用。
