肠道微生物群通过抑制白细胞介素-17在结直肠癌中的抗肿瘤作用参与迷迭香酸的作用。

The involvement of gut microbiota in the anti-tumor effect of carnosic acid via IL-17 suppression in colorectal cancer.

机构信息

School of Life Sciences, Jilin University, Changchun, 130012, China.

Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, 130118, China.

出版信息

Chem Biol Interact. 2022 Sep 25;365:110080. doi: 10.1016/j.cbi.2022.110080. Epub 2022 Aug 1.

DOI:10.1016/j.cbi.2022.110080

PMID:35926579

Abstract

Colorectal cancer (CRC) is a malignant tumor that threatens human health worldwide. Disturbance of the gut microbiota caused by various external factors is one of the leading causes. Carnosic acid (CA) is a phenolic diterpene compound, mainly isolated from rosemary plants, with anti-inflammatory and anti-tumor properties. In this study, we aimed to investigate the role of CA in CRC development and its underlying mechanisms in B6/JGpt-Apc/Gpt (Apc) mice based on the analysis of gut microbiota, serum metabolomics, and tumor proteomics. Enzyme-linked immunosorbent assay (ELISA) and Western blot were performed to confirm the changes in cytokine and protein levels related to inflammation after CA administration. CA regulated the abundance of the gut microbiota, which further caused changes in the production of dl-lactic acid. CA suppressed the inflammatory response by reducing the levels of IL-1β, -6, and -17A. Overall, CA showed anti-CRC properties via modulation of gut microbiota and serum metabolites through NF-κB/STAT3 signaling to inhibit IL-17 expression in Apc mice. These results provide experimental evidence for the future treatment of CRC with CA.

摘要

结直肠癌（CRC）是一种威胁全球人类健康的恶性肿瘤。各种外部因素引起的肠道微生物群失调是其主要原因之一。迷迭香酸（CA）是一种酚类二萜化合物，主要从迷迭香植物中分离得到，具有抗炎和抗肿瘤特性。本研究旨在基于肠道微生物组、血清代谢组学和肿瘤蛋白质组学分析，探讨 CA 在 B6/JGpt-Apc/Gpt（Apc）小鼠 CRC 发展中的作用及其潜在机制。酶联免疫吸附试验（ELISA）和 Western blot 用于确认 CA 给药后与炎症相关的细胞因子和蛋白水平的变化。CA 调节肠道微生物群的丰度，进而导致 dl-乳酸的产生发生变化。CA 通过降低 IL-1β、-6 和 -17A 的水平来抑制炎症反应。总体而言，CA 通过 NF-κB/STAT3 信号通路调节肠道微生物群和血清代谢物，抑制 Apc 小鼠中 IL-17 的表达，从而显示出抗 CRC 特性。这些结果为未来用 CA 治疗 CRC 提供了实验依据。