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

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

doi:10.1186/s12935-020-01305-9

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

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

Authors

Yin Yuan^#^{1

2}, Bo Li^#^{1

2}, Yanbin Kuang³, Shuo Ni⁴, Aoxiang Zhuge^{1

2}, Jing Yang^{1

2}, Longxian Lv^{1

2}, Silan Gu^{1

2}, Ren Yan^{1

2}, Yating Li^{1

2}, Kaicen Wang^{1

2}, Liya Yang^{1

2}, Xueling Zhu^{1

2}, Jingjing Wu^{1

2}, Xiaoyuan Bian^{1

2}, Lanjuan Li^{1

2}

Affiliations

¹ State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003 China.
² Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
³ Department of Respiratory Medicine, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China.
⁴ Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.

^# Contributed equally.

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.

Keywords: Colorectal cancer; GP130; Protein stability; Sodium butyrate; TRAF5.