Lung carcinoids (LCs) comprise well-differentiated neuroendocrine tumors classified as typical (TCs) and atypical (ACs) carcinoids. Unfortunately, curative therapies remain elusive for metastatic LCs, which account for 25–30% of cases. This study evaluated the antitumor activity of axitinib (AXI), a second-generation tyrosine kinase inhibitor selectively targeting vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, VEGFR-3) in human lung TC (NCI-H727, UMC-11, NCI-H835) and AC (NCI-H720) cell lines. In vitro and in vivo (zebrafish) assays were performed following AXI treatment to gather several read-outs about cell viability, cell cycle, the secretion of proangiogenic factors, apoptosis, tumor-induced angiogenesis and migration. AXI demonstrated relevant antitumor activity in human LC cells, with pronounced effects observed in UMC-11 and NCI-H720, characterized by cell cycle perturbation and apoptosis induction. AXI significantly hindered tumor induced-angiogenesis inTg(fli1a:EGFP)y1zebrafish embryos implanted with all LC cell lines and also reduced the invasiveness of NCI-H720 cells, as well as the secretion of several proangiogenic factors. In conclusion, our study provides initial evidence supporting the potential anti-tumor activity of AXI in LC, offering a promising basis for future investigations in mammalian animal models and, eventually, progressing to clinical trials.
肺类癌（LCs）属于分化良好的神经内分泌肿瘤，分为典型类癌（TCs）和非典型类癌（ACs）。遗憾的是，对于占病例25-30%的转移性肺类癌，目前仍缺乏根治性疗法。本研究评估了阿昔替尼（AXI）——一种选择性靶向血管内皮生长因子受体（VEGFR-1、VEGFR-2、VEGFR-3）的第二代酪氨酸激酶抑制剂——在人肺典型类癌细胞系（NCI-H727、UMC-11、NCI-H835）和非典型类癌细胞系（NCI-H720）中的抗肿瘤活性。通过体外及斑马鱼体内实验，检测了AXI处理后细胞活力、细胞周期、促血管生成因子分泌、细胞凋亡、肿瘤诱导血管生成及迁移等多方面指标。AXI在人肺类癌细胞中显示出显著的抗肿瘤活性，其中对UMC-11和NCI-H720细胞系作用尤为明显，表现为细胞周期紊乱和细胞凋亡诱导。在植入所有肺类癌细胞系的Tg(fli1a:EGFP)y1斑马鱼胚胎中，AXI显著抑制了肿瘤诱导的血管生成，同时降低了NCI-H720细胞的侵袭能力及多种促血管生成因子的分泌。总之，本研究为AXI在肺类癌中的潜在抗肿瘤活性提供了初步证据，为未来在哺乳动物模型中的深入研究及最终推进至临床试验奠定了良好基础。
Antitumor Activity of Axitinib in Lung Carcinoids: A Preclinical Study
肿瘤(癌症)患者之家