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阿司匹林通过调节肠球菌和 TIGITTreg 细胞的丰度来预防结直肠癌。

Aspirin prevents colorectal cancer by regulating the abundance of Enterococcus cecorum and TIGITTreg cells.

机构信息

School of Basic Medicine, Ningxia Medical University, Yinchuan, 750004, China.

School of Inspection, Ningxia Medical University, Yinchuan, 750004, China.

出版信息

Sci Rep. 2024 Jun 12;14(1):13592. doi: 10.1038/s41598-024-64447-0.

DOI:10.1038/s41598-024-64447-0
PMID:38867002
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11169407/
Abstract

Although aspirin can reduce the incidence of colorectal cancer (CRC), there is still uncertainty about its significance as a treatment for CRC, and the mechanism of aspirin in CRC is not well understood. In this study, we used aspirin to prevent AOM/DSS-induced CRC in mice, and the anti-CRC efficacy of aspirin was assessed using haematoxylin and eosin (H&E) staining and by determining the mouse survival rate and tumour size. 16S rDNA sequencing, flow cytometry (FCM), and Western blotting were also conducted to investigate the changes in the gut microbiota, tumour immune microenvironment, and apoptotic proteins, respectively. The results demonstrated that aspirin significantly exerted anti-CRC effects in mice. According to 16S rDNA sequencing, aspirin regulated the composition of the gut microbiota and dramatically reduced the abundance of Enterococcus cecorum. FCM demonstrated that there were more CD155 tumour cells and CD4 + CD25 + Treg cells showed increased TIGIT levels. Moreover, increased TIGIT expression on Treg cells is associated with reduced Treg cell functionality. Importantly, the inhibition of Treg cells is accompanied by the promotion of CD19 + GL-7 + B cells, CD8 + T cells, CD4 + CCR4 + Th2 cells, and CD4 + CCR6 + Th17 cells. Overall, aspirin prevents colorectal cancer by regulating the abundance of Enterococcus cecorum and TIGIT + Treg cells.

摘要

尽管阿司匹林可以降低结直肠癌(CRC)的发病率,但关于其作为 CRC 治疗药物的意义仍存在不确定性,且阿司匹林在 CRC 中的作用机制也尚未完全阐明。在本研究中,我们使用阿司匹林预防 AOM/DSS 诱导的小鼠 CRC,并通过苏木精和伊红(H&E)染色以及确定小鼠的存活率和肿瘤大小来评估阿司匹林的抗 CRC 疗效。我们还进行了 16S rDNA 测序、流式细胞术(FCM)和 Western blot,分别研究肠道微生物群、肿瘤免疫微环境和凋亡蛋白的变化。结果表明,阿司匹林在小鼠中显著发挥了抗 CRC 作用。根据 16S rDNA 测序,阿司匹林调节了肠道微生物群的组成,并显著降低了粪肠球菌的丰度。FCM 表明,有更多的 CD155 肿瘤细胞,CD4+CD25+Treg 细胞显示出更高的 TIGIT 水平。此外,Treg 细胞上 TIGIT 的表达增加与 Treg 细胞功能降低有关。重要的是,Treg 细胞的抑制伴随着 CD19+GL-7+B 细胞、CD8+T 细胞、CD4+CCR4+Th2 细胞和 CD4+CCR6+Th17 细胞的增加。总的来说,阿司匹林通过调节粪肠球菌和 TIGIT+Treg 细胞的丰度来预防结直肠癌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd1a/11169407/1624c2f26f0a/41598_2024_64447_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd1a/11169407/93c696f26b0e/41598_2024_64447_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd1a/11169407/ab8770782ffb/41598_2024_64447_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd1a/11169407/7bde7949d648/41598_2024_64447_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd1a/11169407/2fb33027564a/41598_2024_64447_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd1a/11169407/244e0cd2e1c8/41598_2024_64447_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd1a/11169407/1624c2f26f0a/41598_2024_64447_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd1a/11169407/93c696f26b0e/41598_2024_64447_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd1a/11169407/ab8770782ffb/41598_2024_64447_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd1a/11169407/7bde7949d648/41598_2024_64447_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd1a/11169407/2fb33027564a/41598_2024_64447_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd1a/11169407/244e0cd2e1c8/41598_2024_64447_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd1a/11169407/1624c2f26f0a/41598_2024_64447_Fig6_HTML.jpg

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