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HBD 通过 IL-6R/STAT3 信号通路抑制小鼠结肠炎相关癌症的发展。

HBD Inhibits the Development of Colitis-Associated Cancer in Mice via the IL-6R/STAT3 Signaling Pathway.

机构信息

Pi-Wei Institute, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.

School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.

出版信息

Int J Mol Sci. 2019 Mar 1;20(5):1069. doi: 10.3390/ijms20051069.

DOI:10.3390/ijms20051069
PMID:30832202
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6429321/
Abstract

Colitis-associated cancer (CAC) is a malignant disease of the colon that is caused by recurrent episodes of chronic intestinal inflammation. Huangqi Baizhu decoction (HBD) is a classic prescription comprised of and , which are usually used to treat digestive conditions, such as peptic ulcers, colitis, or colorectal carcinoma in clinics. HBD is well known for "tonifying qi and spleen" based on the theories of traditional Chinese medicine, and has the preponderant effect of alleviating chronic intestinal mucosa damage associated with disease. However, the underlying mechanism behind this is still unknown. In the current study, we employed the AOM/DSS mouse model to analyze the effects of HBD on the development of inflammation in colonic carcinoma. The in vivo study showed that HBD could significantly reduce the mortality of mice and control the incidence and size of colonic tumors by inhibiting the IL-6/STAT3 signaling pathway. In vitro, Astragaloside and Atractylenolide (CAA), the main components of HBD, inhibited the proliferation of HCT-116 cells as determined by an MTT assay. Furthermore, CAA notably suppressed the protein expression of IL-6R, STAT3, Survivin, and Cyclin D1 induced by IL-6 in HCT-116 and RAW264.7 cells. These results suggested that HBD exhibits anti-inflammatory and anti-proliferative effects, inhibiting the development of CAC in mice.

摘要

结肠炎相关癌症(CAC)是一种由反复发生的慢性肠道炎症引起的结肠癌恶性疾病。黄芪白术汤(HBD)是一种经典的方剂,由 和 组成,通常用于治疗消化性疾病,如胃溃疡、结肠炎或大肠癌。根据中医理论,HBD 以“补气健脾”而闻名,对缓解与疾病相关的慢性肠黏膜损伤具有优势作用。然而,其潜在的作用机制尚不清楚。在本研究中,我们采用 AOM/DSS 小鼠模型分析了 HBD 对结肠癌炎症发展的影响。体内研究表明,HBD 可通过抑制 IL-6/STAT3 信号通路,显著降低小鼠死亡率,控制结直肠肿瘤的发生率和大小。体外实验表明,黄芪甲苷和白术内酯(CAA),HBD 的主要成分,通过 MTT 测定抑制 HCT-116 细胞的增殖。此外,CAA 显著抑制了 IL-6 在 HCT-116 和 RAW264.7 细胞中诱导的 IL-6R、STAT3、Survivin 和 Cyclin D1 的蛋白表达。这些结果表明,HBD 具有抗炎和抗增殖作用,可抑制 CAC 在小鼠中的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7773/6429321/8270d076a590/ijms-20-01069-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7773/6429321/a70f0327246d/ijms-20-01069-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7773/6429321/8270d076a590/ijms-20-01069-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7773/6429321/a70f0327246d/ijms-20-01069-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7773/6429321/a47d45d080bb/ijms-20-01069-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7773/6429321/bf116fd543d9/ijms-20-01069-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7773/6429321/5c35b93a2e5b/ijms-20-01069-g004.jpg
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