Guo Shanqi, Ma Baojie, Jiang Xingkang, Li Xiaojiang, Jia Yingjie
Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.
Front Pharmacol. 2020 May 5;11:598. doi: 10.3389/fphar.2020.00598. eCollection 2020.
polysaccharides (APS) is a traditional Chinese medicine and have been proved to involve in multiple biological processes, including inflammation, metabolism, and carcinogenics. However, the specific mechanisms by which APS on prostate cancer (PCa) remains largely unknown. In the current study, we found APS greatly inhibited the proliferation and invasion of PCa cells in a dose-dependent and time-dependent manner and . In addition, cellular triglyceride and cholesterol levels were also decreased significantly under APS treatment. Microarray data revealed the SIRT1 expression was markably suppressed under APS exposure. Mechanistic studies demonstrated that over-expression of SIRT1 inhibits the expression and nuclear translocation of SREBP1 activating AMPK phosphorylation to suppress lipid metabolism. Otherwise, knockdown of SIRT1 significantly promotes AMPK/SREBP1 signaling and its associated target genes. Besides, we also found miR-138-5p was greatly inhibited the SIRT1 expression to regulating cell metabolism by targeting its 3'UTR region. To summarize, our findings suggested that APS inhibits tumorigenesis and lipid metabolism through miR-138-5p/SIRT1/SREBP1 pathways in PCa.
多糖（APS）是一种传统中药，已被证明参与多种生物学过程，包括炎症、代谢和致癌作用。然而，APS作用于前列腺癌（PCa）的具体机制仍 largely未知。在当前研究中，我们发现APS以剂量和时间依赖性方式极大地抑制了PCa细胞的增殖和侵袭。此外，在APS处理下，细胞内甘油三酯和胆固醇水平也显著降低。微阵列数据显示，在APS暴露下，SIRT1表达明显受到抑制。机制研究表明，SIRT1的过表达抑制SREBP1的表达和核转位，激活AMPK磷酸化以抑制脂质代谢。否则，敲低SIRT1会显著促进AMPK/SREBP1信号及其相关靶基因。此外，我们还发现miR-138-5p通过靶向其3'UTR区域极大地抑制SIRT1表达以调节细胞代谢。总之，我们的研究结果表明，APS通过miR-138-5p/SIRT1/SREBP1途径抑制PCa中的肿瘤发生和脂质代谢。
