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裙带菜岩藻聚糖通过肠道微生物群和代谢物相互作用抑制肝癌。

Suppression of hepatocellular carcinoma by Ulva lactuca ulvan via gut microbiota and metabolite interactions.

机构信息

College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China; College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China.

School of Basic Medicine, Gannan Medical University, Ganzhou 341000, China.

出版信息

J Adv Res. 2023 Oct;52:103-117. doi: 10.1016/j.jare.2023.04.008. Epub 2023 Apr 17.

DOI:10.1016/j.jare.2023.04.008
PMID:37075862
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10555771/
Abstract

INTRODUCTION

Ulva lactuca polysaccharide (ULP) is green algae extract with numerous biological activities, including anticoagulant, anti-inflammatory, and antiviral effects. However, the inhibitory ability of ULP in the development of hepatocellular carcinoma warrants further studies.

OBJECTIVES

To elucidate the anti-tumor mechanism of ULP action and evaluate its regulatory effect on gut microbiota and metabolism in H22 hepatocellular carcinoma tumor-bearing mice.

METHODS

An H22 tumor-bearing mouse model was established by subcutaneously injecting H22 hepatoma cells. The gut microbiota composition in cecal feces was assessed and subjected to untargeted metabolomic sequencing. The antitumor activity of ULP was verified further by western blot, RT-qPCR, and reactive oxygen species (ROS) assays.

RESULTS

Administration of ULP alleviated tumor growth by modulating the compositions of the gut microbial communities (Tenericutes, Agathobacter, Ruminiclostridium, Parabacteroides, Lactobacillus, and Holdemania) and metabolites (docosahexaenoic acid, uric acid, N-Oleoyl Dopamine, and L-Kynurenine). Mechanistically, ULP promoted ROS production by inhibiting the protein levels of JNK, c-JUN, PI3K, Akt, and Bcl-6, thereby delaying the growth of HepG2 cells.

CONCLUSION

ULP attenuates tumor growth in H22 tumor-bearing mice by modulating gut microbial composition and metabolism. ULP inhibits tumor growth mainly by promoting ROS generation.

摘要

简介

裙带菜多糖(ULP)是一种具有多种生物活性的绿藻提取物,具有抗凝、抗炎和抗病毒作用。然而,ULP 抑制肝细胞癌发展的能力需要进一步研究。

目的

阐明 ULP 作用的抗肿瘤机制,并评估其对 H22 肝癌荷瘤小鼠肠道微生物群和代谢的调节作用。

方法

通过皮下注射 H22 肝癌细胞建立 H22 肿瘤荷瘤小鼠模型。评估盲肠粪便中的肠道微生物群落组成,并进行非靶向代谢组学测序。通过 Western blot、RT-qPCR 和活性氧(ROS)测定进一步验证 ULP 的抗肿瘤活性。

结果

通过调节肠道微生物群落(厚壁菌门、Agathobacter、瘤胃球菌科、拟杆菌属、乳杆菌属和 Holdenmania)和代谢物(二十二碳六烯酸、尿酸、N-Oleoyl Dopamine 和 L-Kynurenine)组成,ULP 缓解了肿瘤生长。在机制上,ULP 通过抑制 JNK、c-JUN、PI3K、Akt 和 Bcl-6 的蛋白水平来促进 ROS 产生,从而延缓 HepG2 细胞的生长。

结论

ULP 通过调节肠道微生物群落组成和代谢来减轻 H22 荷瘤小鼠的肿瘤生长。ULP 主要通过促进 ROS 生成来抑制肿瘤生长。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f57e/10555771/1b350a9fe98c/gr8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f57e/10555771/a879ff62030e/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f57e/10555771/1b350a9fe98c/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f57e/10555771/70617f16a3e6/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f57e/10555771/883766cb100e/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f57e/10555771/d7645f1f3a60/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f57e/10555771/0d341fb4c89d/gr3.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f57e/10555771/5164c33f113e/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f57e/10555771/417229460b8e/gr6.jpg
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