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糖尿病对小鼠结直肠癌模型的影响。

Impacts of pre-existing diabetes mellitus on colorectal cancer in a mice model.

机构信息

Department of Colorectal Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Zhejiang, Quzhou, China.

Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China.

出版信息

Cancer Med. 2023 May;12(10):11641-11650. doi: 10.1002/cam4.5868. Epub 2023 Mar 31.

Abstract

BACKGROUND

Although diabetes mellitus (DM) is regarded as a risk factor of colorectal cancer (CRC), the impacts of pre-existing DM on CRC without drug intervention remain unknown. The purpose of this study was to investigate and analyze the effects of diabetes mellitus (DM) on colorectal cancer (CRC). And, to further explore the influencing factors and the mechanisms of DM affects CRC progression.

METHODS

In this study, we investigated the effects of DM on CRC progression in a streptozotocin-induced DM mice model. Furthermore, we evaluated the change of T cells levels using flow cytometry and indirect immunofluorescence. We assessed the alternation of gut microbiome and the transcriptional response using 16s rRNA sequencing and RNA-seq.

RESULTS

Results showed that the mice survival time was significantly decreased in CRC complicated with DM group (DM-CRC), compared with only tumor bearing mice (CRC group). Furthermore, we found that DM could affect the immune response by changing the infiltration of CD4 T cells, CD8 T cells and mucosal-associated invariant T cell (MAIT) in the CRC progression. In addition, DM could induce gut microbiome dysbiosis and change the transcriptional response in CRC complicated with DM.

CONCLUSION

For the first time, the effects of DM on CRC were systematically characterized in a mice model. Our findings highlight the effects of pre-existing DM on CRC, and these findings should facilitate further studies in exploring and developing potentially targeted therapy for CRC in diabetic patients. Our results suggest that the effects induced by DM should be considered in the treatment for CRC complicated with DM patients.

摘要

背景

尽管糖尿病(DM)被认为是结直肠癌(CRC)的危险因素,但在没有药物干预的情况下,预先存在的 DM 对 CRC 的影响尚不清楚。本研究旨在探讨和分析糖尿病(DM)对结直肠癌(CRC)的影响。并进一步探讨 DM 影响 CRC 进展的影响因素和机制。

方法

在这项研究中,我们在链脲佐菌素诱导的 DM 小鼠模型中研究了 DM 对 CRC 进展的影响。此外,我们使用流式细胞术和间接免疫荧光法评估了 T 细胞水平的变化。我们通过 16s rRNA 测序和 RNA-seq 评估了肠道微生物组的改变和转录反应。

结果

结果表明,与仅患有肿瘤的小鼠(CRC 组)相比,患有 CRC 合并 DM 的小鼠(DM-CRC 组)的存活时间明显缩短。此外,我们发现 DM 可以通过改变 CRC 进展过程中 CD4 T 细胞、CD8 T 细胞和黏膜相关不变 T 细胞(MAIT)的浸润来影响免疫反应。此外,DM 可诱导肠道微生物组失调并改变 DM 合并 CRC 中的转录反应。

结论

这是首次在小鼠模型中系统地描述了 DM 对 CRC 的影响。我们的研究结果强调了预先存在的 DM 对 CRC 的影响,这些发现应该有助于进一步研究探索和开发糖尿病患者潜在的 CRC 靶向治疗。我们的研究结果表明,在治疗 DM 合并 CRC 患者时,应考虑 DM 引起的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2f2/10242856/0b13e8c981b0/CAM4-12-11641-g002.jpg

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