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半乳糖凝集素-9 抑制结肠癌的肿瘤生长。

Galectin‑9 suppresses the tumor growth of colon cancer and .

机构信息

Department of Gastroenterology and Neurology, Kagawa University, Faculty of Medicine, Miki‑cho, Kita‑gun, Kagawa 761‑0793, Japan.

Life Science Research Center, Kagawa University, Faculty of Medicine, Miki‑cho, Kita‑gun, Kagawa 761‑0793, Japan.

出版信息

Oncol Rep. 2021 Jun;45(6). doi: 10.3892/or.2021.8056. Epub 2021 Apr 28.

DOI:10.3892/or.2021.8056
PMID:33907832
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8072828/
Abstract

Colon cancer is the second leading cause of cancer‑related mortality worldwide, and the prognosis of advanced colon cancer has remained poor in recent years. Galectin‑9 (Gal‑9) is a tandem‑repeat type galectin that has recently been shown to exert antiproliferative effects on various types of cancer cells. The present study aimed to assess the effects of Gal‑9 on human colon and colorectal cancer cells and , as well as to evaluate the microRNAs (miRNAs/miRs) associated with the antitumor effects of Gal‑9. We examined the ability of Gal‑9 to inhibit cell proliferation via apoptosis, and the effects of Gal‑9 on cell cycle‑related molecules in various human colon and colorectal cancer cell lines. In addition, Gal‑9‑mediated changes in activated tyrosine kinase receptors and angiogenic molecules were assessed using protein array chips in colon and colorectal cancer cells. Moreover, miRNA array analysis was performed to examine Gal‑9‑induced miRNA expression profiles. We also elucidated if Gal‑9 inhibited tumor growth in a murine model. We found that Gal‑9 suppressed the cell proliferation of colon cancer cell lines and . Our data further revealed that Gal‑9 increased caspase‑cleaved keratin 18 levels in Gal‑9‑treated colon cancer cells. In addition, Gal‑9 enhanced the phosphorylation of ALK, DDR1, and EphA10 proteins. Furthermore, the miRNA expression levels, such as miR‑1246, miR‑15b‑5p, and miR‑1237, were markedly altered by Gal‑9 treatment and . In conclusion, Gal‑9 suppresses the cell proliferation of human colon cancer by inducing apoptosis, and these findings suggest that Gal‑9 can be a potential therapeutic target in the treatment of colon cancer.

摘要

结肠癌是全球癌症相关死亡的第二大主要原因，近年来晚期结肠癌的预后仍然较差。半乳糖凝集素-9（Gal-9）是一种串联重复型半乳糖凝集素，最近已被证明对各种类型的癌细胞具有抗增殖作用。本研究旨在评估 Gal-9 对人结肠和结直肠癌细胞的影响，并评估与 Gal-9 抗肿瘤作用相关的 microRNAs（miRNAs/miRs）。我们研究了 Gal-9 通过细胞凋亡抑制细胞增殖的能力，以及 Gal-9 对各种人结肠和结直肠癌细胞系中细胞周期相关分子的影响。此外，还使用蛋白芯片评估了 Gal-9 介导的激活的酪氨酸激酶受体和血管生成分子的变化。此外，还进行了 miRNA 芯片分析，以检查 Gal-9 诱导的 miRNA 表达谱。我们还阐明了 Gal-9 是否在小鼠模型中抑制肿瘤生长。我们发现 Gal-9 抑制了结肠癌细胞系和的细胞增殖。我们的数据进一步表明，Gal-9 增加了 Gal-9 处理的结肠癌细胞中半胱氨酸天冬氨酸蛋白酶（caspase）切割角蛋白 18 的水平。此外，Gal-9 增强了 ALK、DDR1 和 EphA10 蛋白的磷酸化。此外，Gal-9 处理后，miRNA 的表达水平，如 miR-1246、miR-15b-5p 和 miR-1237，明显改变。总之，Gal-9 通过诱导细胞凋亡抑制人结肠癌的细胞增殖，这些发现表明 Gal-9 可以成为治疗结肠癌的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae30/8072828/e744c6125184/or-45-06-8056-g09.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae30/8072828/0014ec8dfa68/or-45-06-8056-g07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae30/8072828/04b03c33ba9f/or-45-06-8056-g08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae30/8072828/e744c6125184/or-45-06-8056-g09.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae30/8072828/c31ecb52c6f0/or-45-06-8056-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae30/8072828/8c511f70efd9/or-45-06-8056-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae30/8072828/2e05ec678dfe/or-45-06-8056-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae30/8072828/75c3e14005f5/or-45-06-8056-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae30/8072828/4db39d871f7a/or-45-06-8056-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae30/8072828/73b4bfbf69c9/or-45-06-8056-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae30/8072828/c8a7b6c4b6c4/or-45-06-8056-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae30/8072828/0014ec8dfa68/or-45-06-8056-g07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae30/8072828/04b03c33ba9f/or-45-06-8056-g08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae30/8072828/e744c6125184/or-45-06-8056-g09.jpg

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