神经内分泌肿瘤（NETs）是高度血管生成的恶性肿瘤，血管生成可能包括细胞增殖和存活。在具有抗血管生成特性的新兴化合物中，卡波替尼（CAB）表现出了潜在的前景。我们利用体外和体内模型分析了CAB对NETs的抗肿瘤活性。对于细胞培养，我们使用了BON-1、NCI-H727和NCI-H720细胞系。通过FACS分析的丙啶碘化物排除试验，通过手工计数和细胞死亡定量评估细胞存活率。此外，我们还调查了CAB暴露下抗凋亡Myeloid细胞白血病-1蛋白的调节，作为一种可能的适应性细胞存活机制，并与舂亭比较了反应。我们还在小鼠和斑马鱼异种移植肿瘤模型中测试了CAB的活性。卡波替尼在人类NET培养物中表现出对细胞存活率和增殖的剂量依赖和时间依赖性效应，此外还停止了细胞周期进程的转化，这在其他酪氨酸激酶抑制剂中从未报道过。在可移植的斑马鱼模型中，CAB通过胚胎体内大大抑制了NET诱导的血管生成和植入细胞的迁移。在体外和体内模型中，CAB显示出令人鼓舞的NET活性。基于此，我们设想未来的研究将进一步探索这些有希望的线索。

Neuroendocrine tumours (NETs) are highly vascularized malignancies in which angiogenesis may entail cell proliferation and survival. Among the emerging compounds with anti-vascular properties, cabozantinib (CAB) appeared promising. We analyzed the anti-tumor activity of CAB against NETs utilizing in vitro and in vivo models. For cell cultures we used BON-1, NCI-H727 and NCI-H720 cell lines. Cell viability was assessed by manual count coupled with quantification of cell death, performed through FACS analysis as propidium iodide exclusion assay. In addition, we investigated the modulation of the anti-apoptotic Myeloid cell leukemia-1 protein under CAB exposure, as putative adaptive pro-survival mechanism, and compared the responses with sunitinib. The activity of CAB was also tested in mouse and zebrafish xenograft tumor models. Cabozantinib showed a dose-dependent and time-dependent effect on cell viability and proliferation in human NET cultures, besides a halting of cell cycle progression for endoduplication, never reported for other Tyrosine Kinase Inhibitors. In a transplantable zebrafish model, CAB drastically inhibited NET-induced angiogenesis and migration of implanted cells through the embryo body. CAB showed encouraging activity in NETs, both in vitro and in vivo models. On this basis, we envisage future research to further investigate along these promising lines.