吲哚胺 2,3-双加氧酶抑制剂抑制结肠癌细胞迁移、侵袭和上皮-间充质转化。
Indoleamine 2,3-Dioxygenase Inhibitor Suppresses Colon Cancer Cell Migration, Invasion, and Epithelial-Mesenchymal Transition.
机构信息
Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.
Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan
出版信息
Anticancer Res. 2024 Aug;44(8):3337-3342. doi: 10.21873/anticanres.17153.
BACKGROUND/AIM: Indoleamine 2,3-dioxygenase 1 (IDO1) is a key enzyme in tryptophan metabolism and plays an important role in immunosuppression. The effects of IDO1 on tumor invasion and metastasis have been studied in several types of malignancies. However, the role of IDO1 in these steps in colorectal cancer (CRC) has not been elucidated. Therefore, we aimed to investigate the effects of IDO1 on invasion, migration, and epithelial-mesenchymal transition (EMT) in CRC cells.
MATERIALS AND METHODS
All experiments were performed using the DLD-1 colon cancer cell line that expresses IDO1. We conducted a scratch wound healing assay and Boyden chamber assay to investigate the impact of IDO1 on DLD-1 cell migration and invasion, respectively, in the presence and absence of the IDO1 inhibitor L-1-methyl-tryptophan (L-1-MT). Additionally, western blotting was performed to analyze alterations in the expression of EMT-related markers caused by L-1-MT.
RESULTS
High expression of IDO1 was confirmed in the cytoplasm of DLD-1 by immunofluorescence staining. In the scratch wound healing assay, the invasion ability of DLD-1 cells decreased to 62% after treatment with L-1-MT at 1,000 μM for 24 h. In the Boyden chamber assay, the migration of DLD-1 cells was suppressed by 85% after treatment with L-1-MT at 2,500 μM for 24 h. L-1-MT treatment increased the expression level of E-cadherin and decreased the expression levels of vimentin, Snail, and Slug.
CONCLUSION
IDO1 inhibition reduced the invasion and migration ability of IDO1-expressing DLD-1 colon cancer cells, which was accompanied by altered expression of EMT-related proteins. IDO1 could be a potential target for the treatment of advanced CRC.
背景/目的：色氨酸 2,3-双加氧酶 1（IDO1）是色氨酸代谢中的关键酶，在免疫抑制中发挥重要作用。IDO1 对几种恶性肿瘤的侵袭和转移的影响已经进行了研究。然而，IDO1 在结直肠癌（CRC）这些步骤中的作用尚未阐明。因此，我们旨在研究 IDO1 对 CRC 细胞侵袭、迁移和上皮-间充质转化（EMT）的影响。
材料和方法
所有实验均使用表达 IDO1 的 DLD-1 结肠癌细胞系进行。我们进行划痕愈合实验和 Boyden 室实验，分别在存在和不存在 IDO1 抑制剂 L-1-甲基色氨酸（L-1-MT）的情况下，研究 IDO1 对 DLD-1 细胞迁移和侵袭的影响。此外，通过 Western blot 分析 L-1-MT 引起的 EMT 相关标志物表达的变化。
结果
免疫荧光染色证实 DLD-1 细胞质中高表达 IDO1。在划痕愈合实验中，用 1,000 μM 的 L-1-MT 处理 24 小时后，DLD-1 细胞的侵袭能力下降至 62%。在 Boyden 室实验中，用 2,500 μM 的 L-1-MT 处理 24 小时后，DLD-1 细胞的迁移被抑制了 85%。L-1-MT 处理增加了 E-钙黏蛋白的表达水平，降低了波形蛋白、Snail 和 Slug 的表达水平。
结论
IDO1 抑制降低了表达 IDO1 的 DLD-1 结肠癌细胞的侵袭和迁移能力，同时伴随着 EMT 相关蛋白表达的改变。IDO1 可能成为治疗晚期 CRC 的潜在靶点。
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