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

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

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.