Abstract 2825: Two classic TCM formulas suppressed polyp counts in concurrence with improved gut microenvironment, and remodeled gut microbial composition of the Apc<i>Min+</i> mice
Authors: Wenrui Xia, Imran Khan, Xiaoang Li, Guoxin Huang, Wai Kit Leong, Wei lin Liao, W.L. Wendy Hsiao
Journal: Cancer Research (2019)

Abstract Background: In this study we evaluated the anti-cancer effects and gut modulating properties of the two Chinese medicinal formulas, known as HuaiHuaJinYinJiu (SL) and Floris Sophorae Powder (FSP). SL is comprised of Sophorae Flos (HuaiHua) and Lonicerae Japonicae Flos (JinYinHua) and has been traditionally prescribed for carbuncle treatment. The FSP is constituted of Sophorae Flos and Gardenia Jasminoides Ellis (ZhiZi) and has been used for the cure of hemafecia and abdominal pain. Methodology: A total of 27 ApcMin/+ mice were equally divided into three groups and each group were continuously gavage for 28 days with daily dosage of SL (1g/kg), FSP (1g/kg), and water respectively. At the end of the treatments, fecal samples were collected; mice were terminated and sampled for tissues for later investigations. Results: We observed that SL and FSP substantially reduced polyps by 32% and 37% in ApcMin/+ mice, respectively. Additionally, both formulas greatly strengthened the intestinal barrier of the ApcMin/+ mice by enhancing the population of Paneth and goblet cells, up-regulating E-cadherin, and down-regulating N-cadherin expressions. Meanwhile, SL and FSP remodeled the gut microbial composition by facilitating the growth of bacteria belonged to phyla Bacteroidetes and Verrucomicrobia, whereas suppressed the abundance of phyla Fusobacteria and Deferribacteres which are generally known for their pathogenesis. The growth of sulfate-reducing bacteria and bacteria in genus Helicobacter were inhibited in SL and FSP treated mice. We also detected the downregulation of the CagA - which is a cytotoxin-associated gene expressed highly in Helicobacter pylori and has been implicated with CRC development. SL and FSP, on the other hand, facilitated the growth of short-chain fatty (SCFA) producing bacteria that was positively correlated with upregulated expressions of the SCFAs-sensing receptors GPR41, GPR43, and GPR109a. We further found the downregulation of p-AKT, p-ERK, p-STAT3, and beta-catenin in the formula-treated mice. Inflammatory milieu of the SL and FSP treated mice were greatly improved by the polarization of M1 to M2 macrophages and modified with upregulation of anti-inflammatory cytokines (IL-4, IL-10, IL-12) and suppression of pro-inflammatory cytokines (iNOS, IL-1β, IL-17, IL-18, IL-23). Conclusion: Collectively, this study presents strong evidences that the modulation of gut microbiota and the associated metabolites as well as the reversal of the inflammatory gut epithelial barrier might account for the anti-cancer effects of SL and FSP TCM formulas in the ApcMin/+ mice. [This study is supported by Macau FDCT 103/2016/A3 to WLW Hsiao] Citation Format: Wenrui Xia, Imran Khan, Xiaoang Li, Guoxin Huang, Wai Kit Leong, Wei lin Liao, W.L. Wendy Hsiao. Two classic TCM formulas suppressed polyp counts in concurrence with improved gut microenvironment, and remodeled gut microbial composition of the ApcMin+ mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2825.