首页> 外文期刊>European Journal of Inflammation >Inonotus Obliquus Suppresses Proliferation of Colorectal Cancer Cells and Tumor Growth in Mice Models by Downregulation of β-Catenin/NF-κB-Signaling Pathways:
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Inonotus Obliquus Suppresses Proliferation of Colorectal Cancer Cells and Tumor Growth in Mice Models by Downregulation of β-Catenin/NF-κB-Signaling Pathways:

机译:Inonotus obliquus通过下调β-Catenin/NF-κB信号传导通路抑制小鼠模型中结肠直肠癌细胞的增殖和肿瘤生长:

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Chaga mushroom (Inonotus obliquas) has been used as a folk remedy for several illnesses including gastrointestinal disorders. We recently reported the potent anti-inflammatory effect of chaga extract in experimental colitis. However, its effects on colorectal cancer (CRC) have not been clearly elucidated. We investigated the effects of an aqueous extract of Inonotus obliquus (IOAE) in vitro in HCT116 and DLD1 cell lines and in vivo for adenoma in APCMin/+ mice and colitis-associated colon cancer in AOM/DSS-treated mice. Results show that IOAE suppressed the proliferation of both cell lines, and inhibited the growth of intestinal polyps in APCMin/+ and colon tumors in AOM/DSS-treated mice. IOAE induced mitochondrial intrinsic pathway of apoptosis, autophagy, and S phase cell cycle arrest. IOAE suppressed the expression levels of iNOS and Cox-2 and mRNA levels of pro-inflammatory cytokines (IL-6, IL-1β, TNF-a and IFN-γ) in the intestine of mice models. IOAE suppressed the nuclear levels of β-catenin and inhibited its downstream targets (cyclin D1 and c-Myc) along with CRC oncogene CDK8. IOAE inhibited the expression of NF-κB at cytoplasmic and nuclear levels. Our results demonstrate that IOAE possess potent anti-inflammatory and anti-proliferative properties through downregulation of Wnt/β-catenin and NF-κB pathways. Considering recent anticancer approaches involving natural products with minimal side effects, we advocate that Inonotus obliquus could be a beneficial supplement in prevention of colorectal cancer.
机译:Chaga蘑菇(Inonotus obliquas)已被用作针对多种疾病的民间疗法,包括胃肠道疾病。我们最近报道了Chaga提取物在实验性结肠炎中的有效抗炎作用。然而,其对结直肠癌(CRC)的影响尚未明确阐明。我们调查了体外斜肌inoonotus(IOAE)的水提物在HCT116和DLD1细胞系中以及在体内对APCMin / +小鼠中的腺瘤和在AOM / DSS处理的小鼠中与结肠炎相关的结肠癌的影响。结果表明,IOAE抑制了两种细胞系的增殖,并抑制了APCMin / +中的肠息肉和经AOM / DSS处理的小鼠的结肠肿瘤的生长。 IOAE诱导细胞凋亡,自噬和S期细胞周期停滞的线粒体内在途径。 IOAE抑制了小鼠模型肠中iNOS和Cox-2的表达水平以及促炎性细胞因子(IL-6,IL-1β,TNF-α和IFN-γ)的mRNA水平。 IOAE与CRC癌基因CDK8一起抑制了β-catenin的核水平并抑制了其下游靶标(cyclin D1和c-Myc)。 IOAE在细胞质和核水平上抑制NF-κB的表达。我们的结果表明,IOAE通过下调Wnt /β-catenin和NF-κB通路而具有强大的抗炎和抗增殖特性。考虑到最近的涉及天然产物且副作用最小的抗癌方法,我们提倡Inonotus obliquus可以作为预防大肠癌的有益补充。

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