Indoleamine 2,3-Dioxygenase Inhibitor Suppresses Colon Cancer Cell Migration, Invasion, and Epithelial-Mesenchymal Transition.

IF 1.6 4区医学 Q4 ONCOLOGY

Anticancer research Pub Date : 2024-08-01 DOI:10.21873/anticanres.17153

Yumi Yokota, Hiroaki Nozawa, Hirofumi Sonoda, Yuichiro Yokoyama, Shigenobu Emoto, Koji Murono, Kazuhito Sasaki, Soichiro Ishihara

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引用次数: 0

Abstract

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.

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吲哚胺 2,3-二氧化酶抑制剂可抑制结肠癌细胞迁移、侵袭和上皮-间质转化

背景/目的：吲哚胺 2,3-二氧合酶 1（IDO1）是色氨酸代谢过程中的一个关键酶，在免疫抑制中发挥着重要作用。IDO1 对肿瘤侵袭和转移的影响已在多种恶性肿瘤中得到研究。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 细胞的侵袭、迁移和上皮-间质转化（EMT）的影响：所有实验均使用表达 IDO1 的 DLD-1 结肠癌细胞系进行。我们进行了划痕伤口愈合试验和 Boyden 室试验，分别研究 IDO1 在 IDO1 抑制剂 L-1- 甲基色氨酸（L-1-MT）存在和不存在的情况下对 DLD-1 细胞迁移和侵袭的影响。此外，还用 Western 印迹法分析了 L-1-MT 引起的 EMT 相关标记物的表达变化：免疫荧光染色证实 IDO1 在 DLD-1 细胞质中高表达。在划痕伤口愈合试验中，1,000 μM的L-1-MT处理24小时后，DLD-1细胞的侵袭能力下降了62%；在Boyden室试验中，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处理提高了E-cadherin的表达水平，降低了vimentin、Snail和Slug的表达水平：结论：抑制IDO1可降低表达IDO1的DLD-1结肠癌细胞的侵袭和迁移能力，同时改变EMT相关蛋白的表达。IDO1可能是治疗晚期CRC的潜在靶点。

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来源期刊

Anticancer research 医学-肿瘤学

CiteScore

3.70

自引率

10.00%

发文量

566

审稿时长

2 months

期刊介绍： ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed. ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies). Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.