■肺类癌(LCs)是一种起源于支气管肺系统的神经内分泌肿瘤(NET)。LC占所有NET的20-25%,约占肺癌的1-2%。鉴于NETs的高度血管化性质及其过度表达血管生长因子受体(VEGFR)的趋势,抑制血管生成似乎是减缓肿瘤生长和扩散的潜在治疗靶点。本研究评估了阿西替尼(AXI)的长期抗肿瘤活性和相关机制。一种VEGFR靶向药物,在LC细胞系中。
将三种LC细胞系(NCI-H727、UMC-11和NCI-H835)与它们各自的EC50AXI浓度一起孵育6天。在孵化结束时,进行FACS实验和Western印迹分析以检查细胞周期的变化和凋亡的激活。添加了显微镜分析以描述存在时衰老和有丝分裂突变的机制。
■AXI对LC细胞系的主要作用是通过间接DNA损伤阻止肿瘤生长。值得注意的是,AXI在细胞系中以不同的方式触发这种反应,如诱导衰老或有丝分裂灾难。当DNA损伤减轻时,该药物似乎失去了功效,如在NCI-H835细胞中观察到的。
■AXI在LC肿瘤细胞中影响细胞活力和增殖的能力凸显了其作为治疗剂的潜力。DNA损伤的作用以及随之而来的衰老激活似乎是AXI发挥其功能的先决条件。
UNASSIGNED: Lung carcinoids (LCs) are a type of neuroendocrine tumor (NET) that originate in the bronchopulmonary tract. LCs account for 20-25% of all NETs and approximately 1-2% of lung cancers. Given the highly vascularized nature of NETs and their tendency to overexpress vascular growth factor receptors (VEGFR), inhibiting angiogenesis appears as a potential therapeutic target in slowing down tumor growth and spread. This study evaluated the long-term antitumor activity and related mechanisms of axitinib (AXI), a VEGFR-targeting drug, in LC cell lines.
UNASSIGNED: Three LC cell lines (NCI-H727, UMC-11 and NCI-H835) were incubated with their respective EC50 AXI concentrations for 6 days. At the end of the incubation, FACS experiments and Western blot analyses were performed to examine changes in the cell cycle and the activation of apoptosis. Microscopy analyses were added to describe the mechanisms of senescence and mitotic catastrophe when present.
UNASSIGNED: The primary effect of AXI on LC cell lines is to arrest tumor growth through an indirect DNA damage. Notably, AXI triggers this response in diverse manners among the cell lines, such as inducing senescence or mitotic catastrophe. The drug seems to lose its efficacy when the DNA damage is mitigated, as observed in NCI-H835 cells.
UNASSIGNED: The ability of AXI to affect cell viability and proliferation in LC tumor cells highlights its potential as a therapeutic agent. The role of DNA damage and the consequent activation of senescence seem to be a prerequisite for AXI to exert its function.