Background: Progression of Colorectal cancer (CRC) is influenced by single or compounded environmental factors. Accumulating evidence shows that microbiota can influence the outcome of cancer immunotherapy. T cell, one of the main populations of effector immune cells in antitumor immunity, has been considered as a double-edged sword during the progression of CRC. Our previous studies indicate that traditional Chinese herbs (TCM) have potential anticancer effects in improving quality of life and therapeutic effect. However, little is known about the mechanism of TCM formula in cancer prevention. Methods: Here, we used C57BL/6 J Apc Min/+ mice, an animal model of human intestinal tumorigenesis, to investigate the gut bacterial diversity and their mechanisms of action in gastrointestinal adenomas, and to evaluate the effects of Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS) on of colon carcinogenesis in vivo and in vitro. Through humaninto-mice fecal microbiota transplantation (FMT) experiments from YYFZBJS volunteers or control donors, we were able to differentially modulate the tumor microbiome and affect tumor growth as well as tumor immune infiltration.
Pulmonary fibrosis (PF) is a common clinical disease, which results in serious respiratory impairment. Xin Jia Xuan Bai Cheng Qi Decoction (XJXBCQ) is a traditional prescription commonly used in treating lung diseases. We investigate the effect of XJXBCQ against PF and its mechanism via the regulation of TGF-β1/Smad in vitro and in vivo. Materials and methods: XJXBCQ was first extracted and probed for chemical characterization. An PF model in vitro and in vivo was established in rats and in MRC-5 cells. In bleomycin (BLM)-induced rats model, lung function such as peak expiratory flow (PEF), minute ventilation (MV) and hydroxyproline (HYP) were measured; histopathological changes of lung tissue and TGF-β1 in peripheral blood of rats were detected. TGF-β receptor, Smad2 and its phosphorylation expression were tested by Western blot assay in rats model. Then the effects of XJXBCQ on TGF-β1/Smad signal pathway were assessed by Western blot analysis in vitro, and IL-17A and IL-25 levels were evaluated by ELISA in vivo. Results: Our results showed that XJXBCQ significantly enhanced the lung functions, such as PEF, MV and HYP, by reducing the expression level of lung inflammatory cytokine and the content and fibrosis of lung collagen. Moreover, XJXBCQ effectively inhibited TGF-β1, Smad2 and its phosphorylation expression, and the activation of Smad7 in vitro and in vivo. Furthermore, XJXBCQ had an inhibitory effect on the α-smooth muscle actin (α-SMA) and fibronectin (Fn) in vitro and downregulated IL-17A and IL-25 by inhibiting the activation of TGF-β1/Smad signaling pathway in vitro and in vivo. Further, XJXBCQ effectively inhibitied ventilation volume and peak expiratory content remodeling and hydroxyproline content through inhibition of TGF-βRⅡ, Smad2 and its phosphorylation expression, and activation of Smad7 in vivo. Conclusion: XJXBCQ extract had an anti-PF effect in vitro and in vivo, which could be attributed to the inhibition of the expression of p-Smad2 and increase in the expression of Smad7 by regulating the TGF-β1/Smad activity.
Colorectal cancer (CRC) is the third most common solid tumor in the world and shows resistance to several immunotherapies, particularly immune checkpoint blockade which has therapeutic effects on many other types of cancer. T cell (Treg) represents one of the main populations of effector immune cells in antitumor immunity, has been considered as a double-edged sword during the progression of colon carcinogenesis. Our previous studies showed that traditional Chinese herbs had potential anticancer effects in improving the quality of life and therapeutic effect. However, little is known whether the mechanism of TCM formula is depended on the Treg-mediate innate immunity. Here, we used C57BL/6 ApcMin/+ mice, an animal model of human intestinal tumorigenesis, to investigate tumor-associated lymphocyte subsets and the mechanisms of their accumulation into gastrointestinal adenomas, and to evaluate the effects of YYFZBJS on the progression of colon carcinogenesis in vivo and in vitro. Compared to unaffected spleen, intestinal lymphatic, and mesenteric lymph nodes (MLN), accumulated CD4+CD25+ FoxP3 positive Treg cells were reduced after YYFZBJS treatment in ApcMin/+ mice. Treatment with YYFZBJS blocked tumor initiation and progression in the transgenic mouse models (ApcMin/+) with less change of body weight and survival rates. Moreover, YYFZBJS significantly reduced the expression of IL-6, IL-10, TGF-β, and other oncogenes markers such as MMP-2, MMP-9, cyclinD1 and c-Myc in Peripheral Blood and adenomatous tissue. In conclusion, we show that the Treg is involved in CRC development and progression and we identify YYFZBJS as a new potential drug target for the treatment of CRC. Note: This abstract was not presented at the meeting. Citation Format: Hua Sui, Kaijuan Gu, Junze Ren, Haotian Wen, Ting Wang, Jing Hu, Liu Yang, Qing Ji, Qi Li. YYFZBJS ameliorates the progression of colon carcinogenesis in ApcMin/+ mice by inhibiting regulatory T-cell generation [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 4662.
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