癌症是全球第二大死亡原因。抗癌疗法的发展在减轻肿瘤进展和转移方面发挥着至关重要的作用。然而，上皮样血管内皮瘤是一种非常罕见的癌症，具有高度的全身性受累。犬尿氨酸代谢物（包括 L-犬尿氨酸、3-羟基犬尿氨酸、3-羟基邻氨基苯甲酸和喹啉酸）已被证明可以抑制 T 细胞增殖，导致自然杀伤细胞和 T 细胞的细胞生长减少。此外，L-犬尿氨酸等代谢物已被证明可以在体外抑制黑色素瘤细胞的增殖。考虑到这些代谢特性，本研究旨在探讨 l-犬尿氨酸、喹啉酸和犬尿酸对内皮瘤 sEnd-2 细胞和内皮细胞（EA.hy926 细胞）（对照细胞系）的体外影响。评估了两种细胞系在暴露于 1-4mM 范围内的各自犬尿氨酸代谢物 24、48 和 72 小时时对细胞形态、细胞周期进展和细胞凋亡诱导的体外影响。使用非线性回归测定，L-犬尿氨酸、喹啉酸和犬尿酸的半数抑制浓度 (IC50) 分别为 9.17、15.56 和 535.40mM。光学透射光微分干涉对比以及苏木精和伊红染色显示，经 L-犬尿氨酸处理的细胞在中期受阻，形成凋亡小体，细胞密度受损。在经过 l-犬尿氨酸处理的样品中，观察到亚 G1 期细胞数量出现统计学显着增加。据我们所知，这是第一个体外研究，旨在研究犬尿氨酸代谢物对内皮瘤 sEnd-2 细胞的作用机制。可以得出结论，l-犬尿氨酸通过减少细胞生长和增殖以及中期阻滞对内皮瘤 sEnd-2 细胞系发挥抗增殖作用。这些标志表明细胞通过细胞凋亡而死亡。我们将对 l-犬尿氨酸进行进一步的研究，以评估其对体外和体内细胞粘附的影响，因为细胞间粘附已被证明会增加远处器官的转移，因此，抑制粘附可能会导致转移减少。© 2024 作者。细胞生物化学与功能，约翰·威利 (John Wiley) 出版

Cancer is the second leading cause of mortality worldwide. The development of anticancer therapy plays a crucial role in mitigating tumour progression and metastasis. Epithelioid hemangioendothelioma is a very rare cancer, however, with a high systemic involvement. Kynurenine metabolites which include l-kynurenine, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid have been shown to inhibit T-cell proliferation resulting in a decrease in cell growth of natural killer cells and T cells. Furthermore, metabolites such as  l-kynurenine have been shown to inhibit proliferation of melanoma cells in vitro. Considering these metabolite properties, the present study aimed to explore the in vitro effects of  l-kynurenine, quinolinic acid and kynurenic acid on endothelioma sEnd-2 cells and on endothelial (EA. hy926 cells) (control cell line). The in vitro effect at 24, 48, and 72 h exposure to a range of 1-4 mM of the respective kynurenine metabolites on the two cell lines in terms of cell morphology, cell cycle progression and induction of apoptosis was assessed. The half inhibitory concentration (IC50), as determined using nonlinear regression, for  l-kynurenine, quinolinic acid and kynurenic acid was 9.17, 15.56, and 535.40 mM, respectively. Optical transmitted light differential interference contrast and hematoxylin and eosin staining revealed cells blocked in metaphase, formation of apoptotic bodies and compromised cell density in  l-kynurenine-treated cells. A statistically significant increase in the number of cells present in the sub-G1 phase was observed in  l-kynurenine-treated sample. To our knowledge, this was the first in vitro study conducted to investigate the mechanism of action of kynurenine metabolites on endothelioma sEnd-2 cells. It can be concluded that  l-kynurenine exerts an antiproliferative effect on the endothelioma sEnd-2 cell line by decreasing cell growth and proliferation as well as a metaphase block. These hallmarks suggest cell death via apoptosis. Further research will be conducted on  l-kynurenine to assess the effect on cell adhesion in vitro and in vivo as cell-cell adhesion has been shown to increase metastasis to distant organs therefore, the inhibition of adhesion may lead to a decrease in metastasis.© 2024 The Author(s). Cell Biochemistry and Function published by John Wiley & Sons Ltd.