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纤维代谢产物丁酸通过靶向结直肠癌细胞中的TRAF5来降低gp130。

The fiber metabolite butyrate reduces gp130 by targeting TRAF5 in colorectal cancer cells.

作者信息

Yuan Yin, Li Bo, Kuang Yanbin, Ni Shuo, Zhuge Aoxiang, Yang Jing, Lv Longxian, Gu Silan, Yan Ren, Li Yating, Wang Kaicen, Yang Liya, Zhu Xueling, Wu Jingjing, Bian Xiaoyuan, Li Lanjuan

机构信息

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003 China.

Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.

出版信息

Cancer Cell Int. 2020 Jun 3;20:212. doi: 10.1186/s12935-020-01305-9. eCollection 2020.

DOI:10.1186/s12935-020-01305-9
PMID:32518521
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7271451/
Abstract

BACKGROUND

Dietary fiber is effective for colorectal cancer (CRC) treatment. Interleukin-6 (IL-6) and its adaptors are potential targets for CRC therapy. Butyrate, a metabolite of dietary fiber, is a new, highly safe type of targeted drug.

METHODS

In this study, Cell Counting Kit-8 cell viability and wound healing assays, western blot analysis, immunofluorescence staining, and xenograft tumor mouse models were used to evaluate the anticancer effect of butyrate and its possible mechanism in vivo and in vitro.

RESULTS

Dietary fiber and sodium butyrate (NaB) decreased CRC burden by decreasing IL-6 receptor gp130 and blocking IL-6/JAK2/STAT3 axis activation in vitro and in vivo. Furthermore, NaB reduced the gp130 protein level by regulating its degradation rate via targeting TRAF5.

CONCLUSIONS

The fiber metabolite butyrate inhibits CRC development by reducing gp130 via TRAF5.

摘要

背景

膳食纤维对结直肠癌（CRC）治疗有效。白细胞介素-6（IL-6）及其衔接蛋白是CRC治疗的潜在靶点。丁酸盐作为膳食纤维的一种代谢产物，是一种新型、高安全性的靶向药物。

方法

在本研究中，使用细胞计数试剂盒-8细胞活力和伤口愈合试验、蛋白质免疫印迹分析、免疫荧光染色以及异种移植肿瘤小鼠模型来评估丁酸盐的抗癌作用及其在体内和体外的可能机制。

结果

膳食纤维和丁酸钠（NaB）通过降低IL-6受体gp130并在体内和体外阻断IL-6/JAK2/STAT3轴的激活来减轻CRC负担。此外，NaB通过靶向TRAF5调节其降解速率来降低gp130蛋白水平。

结论

纤维代谢产物丁酸盐通过TRAF5降低gp130来抑制CRC的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61b2/7271451/fb59ca938609/12935_2020_1305_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61b2/7271451/75603c2dd7c9/12935_2020_1305_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61b2/7271451/92f9465457eb/12935_2020_1305_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61b2/7271451/54011755c9c4/12935_2020_1305_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61b2/7271451/286a911a1dd5/12935_2020_1305_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61b2/7271451/430ce697eafe/12935_2020_1305_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61b2/7271451/fb59ca938609/12935_2020_1305_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61b2/7271451/75603c2dd7c9/12935_2020_1305_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61b2/7271451/092bc0f2294e/12935_2020_1305_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61b2/7271451/92f9465457eb/12935_2020_1305_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61b2/7271451/54011755c9c4/12935_2020_1305_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61b2/7271451/286a911a1dd5/12935_2020_1305_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61b2/7271451/430ce697eafe/12935_2020_1305_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61b2/7271451/fb59ca938609/12935_2020_1305_Fig7_HTML.jpg

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