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茶多糖通过白细胞介素 6/STAT3 通路抑制结肠炎相关结直肠癌。

Tea Polysaccharides Inhibit Colitis-Associated Colorectal Cancer via Interleukin-6/STAT3 Pathway.

机构信息

New Zealand Institute of Natural Medicine Research , Auckland 2104 , New Zealand.

出版信息

J Agric Food Chem. 2018 May 2;66(17):4384-4393. doi: 10.1021/acs.jafc.8b00710. Epub 2018 Apr 20.

Abstract

The interleukin-6 (IL-6)/signal transducer and activator of transcription (STAT)-3 signaling pathway regulates proliferation and survival of intestinal epithelial cells and has profound impact on the tumorigenesis of colitis-associated cancer (CAC). Tea polysaccharides (TPS) are the major nutraceutical component isolated from tea-leaves and are known to possess antioxidant, anti-inflammatory, and antitumor bioactivities. Here, we investigated the antitumor activities of TPS on CAC using the azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model and IL-6-induced colorectal cancer cell line (CT26) and determined whether TPS exerted its antitumor effects through the IL-6/STAT3 pathway. Results demonstrated that TPS significantly decreased the tumor incidence, tumor size, and markedly inhibited the infiltration of pro-inflammatory cells and the secretion of pro-inflammatory cytokines via balancing cellular microenvironment. Furthermore, we found that TPS suppressed the activation of STAT3 and transcriptionally regulated the expressions of downstream genes including MMP2, cyclin Dl, survivin, and VEGF both in vivo and in vitro. Thus, it was concluded that TPS attenuated the progress of CAC via suppressing IL-6/STAT3 pathway and downstream genes' expressions, which indicated that TPS may be a hopeful antitumor agent for the prevention and treatment of colon cancer.

摘要

白细胞介素 6(IL-6)/信号转导子和转录激活子 3(STAT3)信号通路调节肠道上皮细胞的增殖和存活,并对结肠炎相关癌症(CAC)的发生有深远影响。茶多糖(TPS)是从茶叶中分离得到的主要营养成分,具有抗氧化、抗炎和抗肿瘤的生物活性。在这里,我们使用氧化偶氮甲烷/葡聚糖硫酸钠(AOM/DSS)小鼠模型和 IL-6 诱导的结直肠癌细胞系(CT26)研究了 TPS 对 CAC 的抗肿瘤活性,并确定 TPS 是否通过 IL-6/STAT3 通路发挥其抗肿瘤作用。结果表明,TPS 显著降低了肿瘤发生率、肿瘤大小,并通过平衡细胞微环境显著抑制了促炎细胞的浸润和促炎细胞因子的分泌。此外,我们发现 TPS 抑制了 STAT3 的激活,并在体内和体外转录调控下游基因的表达,包括 MMP2、cyclin D1、survivin 和 VEGF。因此,结论是 TPS 通过抑制 IL-6/STAT3 通路和下游基因的表达来减轻 CAC 的进展,这表明 TPS 可能是预防和治疗结肠癌的有希望的抗肿瘤药物。

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